Is CFAP157 p.Lys174Arg (c.521A>G) pathogenic?

CFAP157 p.Lys174Arg (c.521A>G) is classified Uncertain significance in CFAP157 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: likely benign (0.0774); Ultra-rare (popmax 0.0215%, afr).

How common is CFAP157 p.Lys174Arg (c.521A>G) in the general population?

CFAP157 p.Lys174Arg (c.521A>G) is ultra-rare (popmax 0.0215%, afr) (gnomAD).

What do computational predictors say about CFAP157 p.Lys174Arg (c.521A>G)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

CFAP157 p.Lys174Arg

c.521A>G · rs933870019 · VCV2217603

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0215%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -3.7
Regional constraint	o/e 0.92	unconstrained · MANE · 6,870 bp · p 0.054 · regional, not allelic
Overall
CADD	2.156	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0215% African / African-American · 16/74,320 alleles

Filtering AF 0.0135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.011%

Overall 0.00127% 20/1,577,588 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0215%	4,645
Remaining individualsnot grpmax-eligible	0.0049%	20,410
European (non-Finnish)	8.61e-05%	1,160,974

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.Lys174Arg
Coding: c.521A>G
MANE Select: NM_001012502
dbSNP: rs933870019
Type: single nucleotide variant
Location: chr9:127710688 (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.Lys174Met Uncertain significance ★ ⚠ 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
CFAP157 p.Arg308His Uncertain significance ★ ⚠ same type
CFAP157 p.Arg317Thr 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-lys174arg (accessed [today's date]).

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