Is CABP7 p.Cys175Arg (c.523T>C) pathogenic?

CABP7 p.Cys175Arg (c.523T>C) is classified Uncertain significance in CABP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely benign (0.2164); Ultra-rare (popmax 0.0133%, amr).

How common is CABP7 p.Cys175Arg (c.523T>C) in the general population?

CABP7 p.Cys175Arg (c.523T>C) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CABP7 p.Cys175Arg (c.523T>C)?

AlphaMissense predicts likely benign (score 0.2164) — an in-silico prediction, not a clinical call.

CABP7 p.Cys175Arg

c.523T>C · VCV3994337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2164 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2164	likely benign
REVEL	0.195	benign-leaning
SaProt	LLR -4.97	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.72 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.9	GERP -0.064, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 9,141 bp · p 0.0056 · regional, not allelic
Overall
CADD	22.2	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 0.0133% Admixed American · 8/60,012 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.000559% 9/1,610,012 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,501
African / African-American	0.00133%	75,074

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: CABP7
Protein: p.Cys175Arg
Coding: c.523T>C
MANE Select: NM_182527
Type: single nucleotide variant
Location: chr22:29729444 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 58.35 · 1 PDB

Full CABP7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CABP7 p.Ala192Thr Uncertain significance ★ ⚠ same type
CABP7 p.Ala205Val Uncertain significance ★ ⚠ same type
CABP7 p.Arg135Trp Uncertain significance ★ ⚠ same type
CABP7 p.Arg181His Uncertain significance ★ ⚠ same type
CABP7 p.Arg80Trp Uncertain significance ★ ⚠ same type
CABP7 p.Asn177Lys Uncertain significance ★ ⚠ same type
CABP7 p.Asn50Asp Uncertain significance ★ ⚠ same type
CABP7 p.Asp124Asn 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/cabp7-p-cys175arg (accessed [today's date]).

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