Is CFAP157 p.Thr411Pro (c.1231A>C) pathogenic?

CFAP157 p.Thr411Pro (c.1231A>C) is classified Uncertain significance in CFAP157 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-17). AlphaMissense: likely benign (0.1039); Very rare (popmax 0.00788%, nfe).

How common is CFAP157 p.Thr411Pro (c.1231A>C) in the general population?

CFAP157 p.Thr411Pro (c.1231A>C) is very rare (popmax 0.00788%, nfe) (gnomAD).

What do computational predictors say about CFAP157 p.Thr411Pro (c.1231A>C)?

AlphaMissense predicts likely benign (score 0.1039) — an in-silico prediction, not a clinical call.

CFAP157 p.Thr411Pro

c.1231A>C · VCV3832242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1039 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00788%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1039	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -11.04	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2, phastCons 0.075
Regional constraint	o/e 0.92	unconstrained · MANE · 6,870 bp · p 0.054 · regional, not allelic
Overall
CADD	13.72	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 0.00788% European (non-Finnish) · 93/1,180,014 alleles

Filtering AF 0.00656% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00608%

Overall 0.00595% 96/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00788%	12,688
Remaining individualsnot grpmax-eligible	0.0032%	31,244
African / African-American	0.00133%	74,928

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: CFAP157
Protein: p.Thr411Pro
Coding: c.1231A>C
MANE Select: NM_001012502
Type: single nucleotide variant
Location: chr9:127712802 (GRCh38)
Gene constraint: LOEUF 0.998 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.75

Full CFAP157 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CFAP157 p.Ala121Val Uncertain significance ★ ⚠ same type
CFAP157 p.Ala365Val Uncertain significance ★ ⚠ same type
CFAP157 p.Ala420Glu Uncertain significance ★ ⚠ same type
CFAP157 p.Arg155Gln Uncertain significance ★ ⚠ same type
CFAP157 p.Arg155Trp Uncertain significance ★ ⚠ same type
CFAP157 p.Arg308His Uncertain significance ★ ⚠ same type
CFAP157 p.Arg317Thr Uncertain significance ★ ⚠ same type
CFAP157 p.Arg348Trp 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/cfap157-p-thr411pro (accessed [today's date]).

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