Is CABP7 p.Arg80Trp (c.238C>T) pathogenic?

CABP7 p.Arg80Trp (c.238C>T) is classified Uncertain significance in CABP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-09). AlphaMissense: likely pathogenic (0.9677); Very rare (popmax 0.00441%, sas).

How common is CABP7 p.Arg80Trp (c.238C>T) in the general population?

CABP7 p.Arg80Trp (c.238C>T) is very rare (popmax 0.00441%, sas) (gnomAD).

What do computational predictors say about CABP7 p.Arg80Trp (c.238C>T)?

AlphaMissense predicts likely pathogenic (score 0.9677) — an in-silico prediction, not a clinical call.

CABP7 p.Arg80Trp

c.238C>T · VCV3483875

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9677 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9677	likely pathogenic
REVEL	0.587	indeterminate
SaProt	LLR -13.99	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 1	GERP -1.3, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 9,141 bp · p 0.0056 · regional, not allelic
Overall
CADD	25.9	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 0.00441% South Asian · 4/90,612 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000895%

Overall 0.00149% 24/1,610,232 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00803%	12,458
South Asiangrpmax	0.00441%	22,653
East Asian	0.00224%	44,732
African / African-American	0.00134%	74,802
European (non-Finnish)	0.0011%	90,635

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg80Trp
Coding: c.238C>T
MANE Select: NM_182527
Type: single nucleotide variant
Location: chr22:29727790 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 58.35 · 1 PDB
Residue 80: an α-helix; the ef-hand 2 domain

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.Asn177Lys Uncertain significance ★ ⚠ same type
CABP7 p.Asn50Asp Uncertain significance ★ ⚠ same type
CABP7 p.Asp124Asn Uncertain significance ★ ⚠ same type
CABP7 p.Asp84Gly 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-arg80trp (accessed [today's date]).

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