Is CFAP77 p.Arg118Gln (c.353G>A) pathogenic?

CFAP77 p.Arg118Gln (c.353G>A) is classified Uncertain significance in CFAP77 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.1353); Ultra-rare (popmax 0.0495%, mid).

How common is CFAP77 p.Arg118Gln (c.353G>A) in the general population?

CFAP77 p.Arg118Gln (c.353G>A) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about CFAP77 p.Arg118Gln (c.353G>A)?

AlphaMissense predicts likely benign (score 0.1353) — an in-silico prediction, not a clinical call.

CFAP77 p.Arg118Gln

c.353G>A · rs750950057 · VCV2490450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1353 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1353	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -12.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 0.86, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 162 kb · p 0.31 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R154Q vs ClinVar R118Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00718%

Overall 0.00123% 18/1,461,872 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
South Asian	0.00549%	18,216
Remaining individualsnot grpmax-eligible	0.0032%	31,254
Admixed American	0.00167%	60,028
Finnishnot grpmax-eligible	0.00156%	64,028
European (non-Finnish)	0.000508%	196,674

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.Arg118Gln
Coding: c.353G>A
MANE Select: NM_001282957
dbSNP: rs750950057
Type: single nucleotide variant
Location: chr9:132499429 (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.Arg125Cys 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-arg118gln (accessed [today's date]).

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