Is CFAP77 p.Leu92Pro (c.275T>C) pathogenic?

CFAP77 p.Leu92Pro (c.275T>C) is classified Uncertain significance in CFAP77 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-30). AlphaMissense: likely benign (0.1673); Rare (popmax 0.144%, nfe).

How common is CFAP77 p.Leu92Pro (c.275T>C) in the general population?

CFAP77 p.Leu92Pro (c.275T>C) is rare (popmax 0.144%, nfe) (gnomAD).

What do computational predictors say about CFAP77 p.Leu92Pro (c.275T>C)?

AlphaMissense predicts likely benign (score 0.1673) — an in-silico prediction, not a clinical call.

CFAP77 p.Leu92Pro

c.275T>C · rs148397666 · VCV2509559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1673 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.144%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1673	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -6.19	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 1.2	GERP -0.13, phastCons 0.5
Regional constraint	o/e 0.95	unconstrained · MANE · 162 kb · p 0.31 · regional, not allelic
Overall
CADD	15.73	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 L128P vs ClinVar L92P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.144% European (non-Finnish) · 1,697/1,177,988 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.136%

Overall 0.112% 1,801/1,610,248 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.144%	694
Remaining individualsnot grpmax-eligible	0.0722%	1,385
Finnishnot grpmax-eligible	0.0376%	2,658
African / African-American	0.032%	3,127
Admixed American	0.0168%	5,962
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,444

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.Leu92Pro
Coding: c.275T>C
MANE Select: NM_001282957
dbSNP: rs148397666
Type: single nucleotide variant
Location: chr9:132498774 (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-leu92pro (accessed [today's date]).

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