Is CFAP77 p.Arg142His (c.425G>A) pathogenic?

CFAP77 p.Arg142His (c.425G>A) is classified Uncertain significance in CFAP77 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-26). AlphaMissense: likely benign (0.0727); Ultra-rare (popmax 0.0386%, afr).

How common is CFAP77 p.Arg142His (c.425G>A) in the general population?

CFAP77 p.Arg142His (c.425G>A) is ultra-rare (popmax 0.0386%, afr) (gnomAD).

What do computational predictors say about CFAP77 p.Arg142His (c.425G>A)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

CFAP77 p.Arg142His

c.425G>A · VCV3266540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -12.51	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 5.7	GERP -2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 162 kb · p 0.31 · regional, not allelic
Overall
CADD	18.54	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 R178H vs ClinVar R142H) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0386% African / African-American · 29/75,046 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0238%

Overall 0.0026% 42/1,614,186 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0386%	2,588
Middle Eastern	0.0165%	6,062
East Asian	0.00669%	14,959
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
Admixed American	0.00333%	30,017
Remaining individualsnot grpmax-eligible	0.0032%	31,253
South Asian	0.0011%	91,084
European (non-Finnish)	0.000254%	393,343

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.Arg142His
Coding: c.425G>A
MANE Select: NM_001282957
Type: single nucleotide variant
Location: chr9:132499501 (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-arg142his (accessed [today's date]).

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