Is CFAP53 p.Asp85Asn (c.253G>A) pathogenic?

CFAP53 p.Asp85Asn (c.253G>A) is classified Uncertain significance in CFAP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-13). AlphaMissense: likely benign (0.2166); Very rare (popmax 0.00891%, eas); Associated with Inborn genetic diseases.

What condition is associated with CFAP53 p.Asp85Asn (c.253G>A)?

CFAP53 p.Asp85Asn (c.253G>A) is associated with Inborn genetic diseases, heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Asp85Asn (c.253G>A) in the general population?

CFAP53 p.Asp85Asn (c.253G>A) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CFAP53 p.Asp85Asn (c.253G>A)?

AlphaMissense predicts likely benign (score 0.2166) — an in-silico prediction, not a clinical call.

CFAP53 p.Asp85Asn

c.253G>A · rs764782179 · VCV959683

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2166 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2166	likely benign
REVEL	0.062	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.2	GERP 0.97, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,900 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,614,066 alleles · very rare

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.Asp85Asn
Coding: c.253G>A
MANE Select: NM_145020
dbSNP: rs764782179
Type: single nucleotide variant
Location: chr18:50262036 (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 85: a UniProt-annotated variant site (in htx6; uncertain significance; no overt effects on the structure or function of respiratory cilia)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: heterotaxy, visceral, 6, autosomal

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.Arg470His 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

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-asp85asn (accessed [today's date]).

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