Is CFAP77 p.Arg90Gln (c.269G>A) pathogenic?

CFAP77 p.Arg90Gln (c.269G>A) is classified Uncertain significance in CFAP77 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-11). AlphaMissense: likely benign (0.1067); Ultra-rare (popmax 0.0177%, sas).

How common is CFAP77 p.Arg90Gln (c.269G>A) in the general population?

CFAP77 p.Arg90Gln (c.269G>A) is ultra-rare (popmax 0.0177%, sas) (gnomAD).

What do computational predictors say about CFAP77 p.Arg90Gln (c.269G>A)?

AlphaMissense predicts likely benign (score 0.1067) — an in-silico prediction, not a clinical call.

CFAP77 p.Arg90Gln

c.269G>A · VCV3832435

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1067 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0177%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1067	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -6.49	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 3.3	GERP 0.96, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 162 kb · p 0.31 · regional, not allelic
Overall
CADD	19.99	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R126Q vs ClinVar R90Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0177% South Asian · 16/90,382 alleles

Filtering AF 0.0111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00905%

Overall 0.00453% 73/1,610,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0177%	5,649
African / African-American	0.00534%	18,726
Admixed American	0.00503%	19,891
European (non-Finnish)	0.00407%	24,550
Remaining individualsnot grpmax-eligible	0.00321%	31,173

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: CFAP77
Protein: p.Arg90Gln
Coding: c.269G>A
MANE Select: NM_001282957
Type: single nucleotide variant
Location: chr9:132498768 (GRCh38)
Gene constraint: LOEUF 1.092 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.75 · 2 PDB

Full CFAP77 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP77 c.196-16283C>G Uncertain significance ★ ⚠ same type
CFAP77 c.196-16315C>T Uncertain significance ★ ⚠ same type
CFAP77 c.196-16327A>G Uncertain significance ★ ⚠ same type
CFAP77 c.196-16333C>T Uncertain significance ★ ⚠ same type
CFAP77 c.196-16357C>T Uncertain significance ★ ⚠ same type
CFAP77 p.Ala127Val Uncertain significance ★ ⚠ same type
CFAP77 p.Ala256Val Uncertain significance ★ ⚠ same type
CFAP77 p.Arg118Gln Uncertain significance ★ ⚠ same type

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/cfap77-p-arg90gln (accessed [today's date]).

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