Is CFAP96 p.Glu285Lys (c.853G>A) pathogenic?

CFAP96 p.Glu285Lys (c.853G>A) is classified Uncertain significance in CFAP96 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely benign (0.1075); Ultra-rare (popmax 0.0655%, nfe).

How common is CFAP96 p.Glu285Lys (c.853G>A) in the general population?

CFAP96 p.Glu285Lys (c.853G>A) is ultra-rare (popmax 0.0655%, nfe) (gnomAD).

What do computational predictors say about CFAP96 p.Glu285Lys (c.853G>A)?

AlphaMissense predicts likely benign (score 0.1075) — an in-silico prediction, not a clinical call.

CFAP96 p.Glu285Lys

c.853G>A · rs201058690 · VCV2373634

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1075 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0655%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1075	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -8.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.32	donor loss · deltas
Constraint at this position
Conservation	phyloP 1.1	GERP -2.4, phastCons 0.53
Regional constraint	o/e 0.92	unconstrained · MANE · 20 kb · p 0.15 · regional, not allelic
Overall
CADD	8.014	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0655% European (non-Finnish) · 751/1,146,952 alleles

Filtering AF 0.0615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.06%

Overall 0.051% 791/1,551,456 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0655%	1,527
Remaining individualsnot grpmax-eligible	0.0449%	2,225
Admixed American	0.0137%	7,279
African / African-American	0.00822%	12,172

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: CFAP96
Protein: p.Glu285Lys
Coding: c.853G>A
MANE Select: NM_001114357
dbSNP: rs201058690
Type: single nucleotide variant
Location: chr4:185445102 (GRCh38)
Structure: AlphaFold pLDDT 74.34

Full CFAP96 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UFSP2 p.Ile13Thr Uncertain significance ★★ ⚠ same type
UFSP2 p.Leu85Val Uncertain significance ★★ ⚠ same type
UFSP2 c.333+11T>C Benign ★★ same type
UFSP2 c.-33C>T Benign ★★ same type
UFSP2 p.Asn235Ser Benign/Likely benign ★★ same type
UFSP2 p.Glu93= Benign/Likely benign ★★ same type
UFSP2 p.Ser79= Benign ★★ same type
UFSP2 p.Thr76= Benign/Likely benign ★★ 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/cfap96-p-glu285lys (accessed [today's date]).

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