Is CFAP99 p.Ala423Thr (c.1267G>A) pathogenic?

CFAP99 p.Ala423Thr (c.1267G>A) is classified Uncertain significance in CFAP99 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-17). Very rare (popmax 0.0014%, nfe).

How common is CFAP99 p.Ala423Thr (c.1267G>A) in the general population?

CFAP99 p.Ala423Thr (c.1267G>A) is very rare (popmax 0.0014%, nfe) (gnomAD).

CFAP99 p.Ala423Thr

c.1267G>A · VCV4001714

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0014%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.168	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 36 kb · p 0.016 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0014% European (non-Finnish) · 16/1,146,840 alleles

Filtering AF 0.000826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00104% 16/1,535,830 alleles · very rare

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: CFAP99
Protein: p.Ala423Thr
Coding: c.1267G>A
MANE Select: NM_001193282
Type: single nucleotide variant
Location: chr4:2458828 (GRCh38)
Gene constraint: LOEUF 1.203 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.28

Full CFAP99 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP99 p.Ala255Thr Uncertain significance ★ same type
CFAP99 p.Ala307Thr Uncertain significance ★ same type
CFAP99 p.Ala366Thr Uncertain significance ★ same type
CFAP99 p.Ala369Gly Uncertain significance ★ same type
CFAP99 p.Ala396Val Uncertain significance ★ same type
CFAP99 p.Ala428Thr Uncertain significance ★ same type
CFAP99 p.Ala450Ser Uncertain significance ★ same type
CFAP99 p.Ala450Val 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/cfap99-p-ala423thr (accessed [today's date]).

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