Is CFAP299 p.Glu4Asp (c.12A>T) pathogenic?

CFAP299 p.Glu4Asp (c.12A>T) is classified Likely benign in CFAP299 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-04). AlphaMissense: likely benign (0.0736); Ultra-rare (popmax 0.0467%, amr).

How common is CFAP299 p.Glu4Asp (c.12A>T) in the general population?

CFAP299 p.Glu4Asp (c.12A>T) is ultra-rare (popmax 0.0467%, amr) (gnomAD).

What do computational predictors say about CFAP299 p.Glu4Asp (c.12A>T)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

CFAP299 p.Glu4Asp

c.12A>T · rs769950458 · VCV3143442

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0467%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.38	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 -1.4	GERP -5.1
Regional constraint	o/e 1.12	unconstrained · MANE · 628 kb · p 0.045 · regional, not allelic
Overall
CADD	7.193	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 0.0467% Admixed American · 28/60,014 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0286%

Overall 0.00186% 30/1,611,142 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0467%	2,143
Remaining individualsnot grpmax-eligible	0.0016%	62,398
African / African-American	0.00134%	74,900

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: CFAP299
Protein: p.Glu4Asp
Coding: c.12A>T
MANE Select: NM_152770
dbSNP: rs769950458
Type: single nucleotide variant
Location: chr4:80335780 (GRCh38)
Gene constraint: LOEUF 1.358 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.40 · 2 PDB

Full CFAP299 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP299 c.333+25162G>C Uncertain significance ★ same type
CFAP299 p.His227Gln Uncertain significance ★ ⚠ same type
CFAP299 p.Thr84Ser Uncertain significance ★ ⚠ same type
CFAP299 p.Pro174= Likely benign ★ same type
CFAP299 p.Thr96Met 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/cfap299-p-glu4asp (accessed [today's date]).

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