Is CFAP53 p.Arg102His (c.305G>A) pathogenic?

CFAP53 p.Arg102His (c.305G>A) is classified Benign/Likely benign in CFAP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-10-22). AlphaMissense: likely benign (0.1631); Low-frequency (popmax 2.32%, afr); Associated with heterotaxy, visceral, 6, autosomal.

What condition is associated with CFAP53 p.Arg102His (c.305G>A)?

CFAP53 p.Arg102His (c.305G>A) is associated with heterotaxy, visceral, 6, autosomal (ClinVar).

How common is CFAP53 p.Arg102His (c.305G>A) in the general population?

CFAP53 p.Arg102His (c.305G>A) is low-frequency (popmax 2.32%, afr) (gnomAD).

What do computational predictors say about CFAP53 p.Arg102His (c.305G>A)?

AlphaMissense predicts likely benign (score 0.1631) — an in-silico prediction, not a clinical call.

CFAP53 p.Arg102His

c.305G>A · rs76722120 · VCV262551

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1631 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.32%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

heterotaxy, visceral, 6, autosomal

Computational evidence

Protein change
AlphaMissense	0.1631	likely benign
REVEL	0.134	moderately benign-leaning
SaProt	LLR -9.30	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 2.2	GERP 1.9, phastCons 0.99
Regional constraint	o/e 1.02	unconstrained · MANE · 39 kb · p 0.59 · regional, not allelic
Overall
CADD	26.7	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 2.32% African / African-American · 1,481/63,770 alleles

Filtering AF 2.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.18%

Overall 0.123% 1,799/1,461,570 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.32%	43
Admixed American	0.241%	415
Remaining individualsnot grpmax-eligible	0.184%	544
Middle Eastern	0.0924%	1,082
Ashkenazi Jewishnot grpmax-eligible	0.0399%	2,504
South Asian	0.022%	4,554
European (non-Finnish)	0.0085%	11,771
Finnishnot grpmax-eligible	0.00787%	12,714
East Asian	0.00516%	19,378

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.Arg102His
Coding: c.305G>A
MANE Select: NM_145020
dbSNP: rs76722120
Type: single nucleotide variant
Location: chr18:50261232 (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 102: 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

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

Similar variants

CFAP53 p.Arg102Cys Uncertain significance ★ ⚠ same residue
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

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-arg102his (accessed [today's date]).

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