Is CFAP61 p.Glu90Ala (c.269A>C) pathogenic?

CFAP61 p.Glu90Ala (c.269A>C) is classified Conflicting classifications of pathogenicity in CFAP61 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-18). AlphaMissense: likely benign (0.1544); Ultra-rare (popmax 0.0413%, afr).

How common is CFAP61 p.Glu90Ala (c.269A>C) in the general population?

CFAP61 p.Glu90Ala (c.269A>C) is ultra-rare (popmax 0.0413%, afr) (gnomAD).

What do computational predictors say about CFAP61 p.Glu90Ala (c.269A>C)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

CFAP61 p.Glu90Ala

c.269A>C · rs199790525 · VCV2652230

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0413%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -7.36	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 304 kb · p 0.21 · regional, not allelic
Overall
CADD	23.5	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 0.0413% African / African-American · 31/75,042 alleles

Filtering AF 0.0298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.026%

Overall 0.00229% 37/1,614,104 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0413%	2,421
Remaining individualsnot grpmax-eligible	0.0096%	10,418

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: CFAP61
Protein: p.Glu90Ala
Coding: c.269A>C
MANE Select: NM_015585
dbSNP: rs199790525
Type: single nucleotide variant
Location: chr20:20070979 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.86 · 1 PDB

Full CFAP61 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP61 p.Glu90Gln Uncertain significance ★ ⚠ same residue
CFAP61 p.Arg552Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
CFAP61 c.3125-1G>C Likely pathogenic ★ same type
CFAP61 p.Arg283Ter Pathogenic ★ same type
CFAP61 p.Val755Ala Likely pathogenic ★ ⚠ same type
CFAP61 p.Ala1026Asp Uncertain significance ★ ⚠ same type
CFAP61 p.Ala1081Gly Uncertain significance ★ ⚠ same type
CFAP61 p.Ala1081Ser 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/cfap61-p-glu90ala (accessed [today's date]).

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