Is CFAP53 p.Glu294Lys (c.880G>A) pathogenic?

CFAP53 p.Glu294Lys (c.880G>A) is classified Benign in CFAP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-30). AlphaMissense: likely benign (0.0921); Common (popmax 38.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Glu294Lys (c.880G>A)?

CFAP53 p.Glu294Lys (c.880G>A) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

What do computational predictors say about CFAP53 p.Glu294Lys (c.880G>A)?

AlphaMissense predicts likely benign (score 0.0921) — an in-silico prediction, not a clinical call.

CFAP53 p.Glu294Lys

Q: How common is CFAP53 p.Glu294Lys (c.880G>A) in the general population?

CFAP53 p.Glu294Lys (c.880G>A) is common (popmax 38.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.880G>A · rs35193847 · VCV262560

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0921 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 38.6%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
AlphaMissense	0.0921	likely benign
REVEL	0.089	moderately benign-leaning
SaProt	LLR -8.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.79, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 38.6% European (non-Finnish) · 455,279/1,179,850 alleles

Filtering AF 38.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.5%

Overall 34.8% 561,431/1,613,874 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	41.6%	2
Finnishnot grpmax-eligible	39.2%	3
European (non-Finnish)grpmax	38.6%	3
Ashkenazi Jewishnot grpmax-eligible	33.1%	3
Remaining individualsnot grpmax-eligible	33%	3
Middle Eastern	32.8%	3
South Asian	26.8%	4
Admixed American	19.5%	5
African / African-American	13.1%	8
East Asian	5.21%	19

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CFAP53
Protein: p.Glu294Lys
Coding: c.880G>A
MANE Select: NM_145020
dbSNP: rs35193847
Type: single nucleotide variant
Location: chr18:50250874 (GRCh38)
Gene constraint: LOEUF 1.282 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.17 · 2 PDB
Residue 294: the trichohyalin-plectin-homology domain; a UniProt-annotated variant site (in htx6; uncertain significance; no overt effects on the structure or function of respiratory cilia); a UniProt-annotated variant site (in)

Full CFAP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

heterotaxy, visceral, 6, autosomal — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CFAP53 p.Ala185Thr Uncertain significance ★★ ⚠ same condition
CFAP53 p.Ala385Ser Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg158Gly Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg257Cys Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505His Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Leu Uncertain significance ★★ ⚠ same condition
CFAP53 p.Arg505Ser Uncertain significance ★★ ⚠ same condition
CFAP53 p.Asp85Asn Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cfap53-p-glu294lys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown