Is CFAP126 p.Leu19Pro (c.56T>C) pathogenic?

CFAP126 p.Leu19Pro (c.56T>C) is classified Uncertain significance in CFAP126 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). AlphaMissense: likely pathogenic (0.7938); Ultra-rare (popmax 0.0681%, afr).

How common is CFAP126 p.Leu19Pro (c.56T>C) in the general population?

CFAP126 p.Leu19Pro (c.56T>C) is ultra-rare (popmax 0.0681%, afr) (gnomAD).

What do computational predictors say about CFAP126 p.Leu19Pro (c.56T>C)?

AlphaMissense predicts likely pathogenic (score 0.7938) — an in-silico prediction, not a clinical call.

CFAP126 p.Leu19Pro

c.56T>C · rs150422177 · VCV3143324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7938 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0681%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.7938	likely pathogenic · top 10% in CFAP126
REVEL	0.466	indeterminate
SaProt	LLR -15.65	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
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 0.81	unconstrained · MANE · 2,900 bp · p 0.0048 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0681% African / African-American · 51/74,924 alleles

Filtering AF 0.0531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00328% 53/1,614,018 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0681%	1,469
European (non-Finnish)	0.000169%	589,998

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.Leu19Pro
Coding: c.56T>C
MANE Select: NM_001013625
dbSNP: rs150422177
Type: single nucleotide variant
Location: chr1:161366473 (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-leu19pro (accessed [today's date]).

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