Is CFAP126 p.Pro76Thr (c.226C>A) pathogenic?

CFAP126 p.Pro76Thr (c.226C>A) is classified Uncertain significance in CFAP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-04). AlphaMissense: ambiguous (0.3766); Ultra-rare (popmax 0.012%, nfe).

How common is CFAP126 p.Pro76Thr (c.226C>A) in the general population?

CFAP126 p.Pro76Thr (c.226C>A) is ultra-rare (popmax 0.012%, nfe) (gnomAD).

What do computational predictors say about CFAP126 p.Pro76Thr (c.226C>A)?

AlphaMissense predicts ambiguous (score 0.3766) — an in-silico prediction, not a clinical call.

CFAP126 p.Pro76Thr

c.226C>A · rs148395391 · VCV2412099

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3766 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3766	ambiguous
REVEL	0.162	moderately benign-leaning
SaProt	LLR -8.24	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 2,900 bp · p 0.0048 · regional, not allelic
Overall
CADD	25.5	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 0.012% European (non-Finnish) · 141/1,179,716 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00973%

Overall 0.00942% 152/1,613,378 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.012%	8,367
Remaining individualsnot grpmax-eligible	0.00641%	15,612
African / African-American	0.00534%	18,722
Admixed American	0.00167%	59,856
Finnishnot grpmax-eligible	0.00156%	64,014
South Asian	0.0011%	91,018

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: CFAP126
Protein: p.Pro76Thr
Coding: c.226C>A
MANE Select: NM_001013625
dbSNP: rs148395391
Type: single nucleotide variant
Location: chr1:161365648 (GRCh38)
Gene constraint: LOEUF 1.591 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.17 · 2 PDB

Full CFAP126 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP126 p.Ala90Val Uncertain significance ★ ⚠ same type
CFAP126 p.Arg46Cys Uncertain significance ★ ⚠ same type
CFAP126 p.Arg46His Uncertain significance ★ ⚠ same type
CFAP126 p.Arg84Cys Uncertain significance ★ ⚠ same type
CFAP126 p.Arg84His Uncertain significance ★ ⚠ same type
CFAP126 p.Asp156Asn Uncertain significance ★ ⚠ same type
CFAP126 p.Cys110Ser Uncertain significance ★ ⚠ same type
CFAP126 p.Gln172Glu 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/cfap126-p-pro76thr (accessed [today's date]).

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