Is CFAP157 p.Lys4Glu (c.10A>G) pathogenic?

CFAP157 p.Lys4Glu (c.10A>G) is classified Uncertain significance in CFAP157 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.6109); Ultra-rare (popmax 0.0201%, eas).

How common is CFAP157 p.Lys4Glu (c.10A>G) in the general population?

CFAP157 p.Lys4Glu (c.10A>G) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

What do computational predictors say about CFAP157 p.Lys4Glu (c.10A>G)?

AlphaMissense predicts likely pathogenic (score 0.6109) — an in-silico prediction, not a clinical call.

CFAP157 p.Lys4Glu

c.10A>G · VCV4226843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6109 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6109	likely pathogenic
REVEL	0.301	indeterminate
SaProt	LLR -11.01	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 6.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 6,870 bp · p 0.054 · regional, not allelic
Overall
CADD	24.1	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 0.0201% East Asian · 9/44,866 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.000558% 9/1,613,586 alleles · ultra-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: CFAP157
Protein: p.Lys4Glu
Coding: c.10A>G
MANE Select: NM_001012502
Type: single nucleotide variant
Location: chr9:127707041 (GRCh38)
Gene constraint: LOEUF 0.998 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.75
Residue 4: the 'disordered' region

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

Similar variants

CFAP157 p.Lys4Gln Uncertain significance ★ ⚠ same residue
PTRH1 p.Gly4Asp Uncertain significance ★ ⚠ same residue
PTRH1 p.Gly4Arg Likely benign ★ same residue
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

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-lys4glu (accessed [today's date]).

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