Is CABP7 p.Gly49Ser (c.145G>A) pathogenic?

CABP7 p.Gly49Ser (c.145G>A) is classified Uncertain significance in CABP7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.6633); Very rare (popmax 0.0072%, nfe).

How common is CABP7 p.Gly49Ser (c.145G>A) in the general population?

CABP7 p.Gly49Ser (c.145G>A) is very rare (popmax 0.0072%, nfe) (gnomAD).

What do computational predictors say about CABP7 p.Gly49Ser (c.145G>A)?

AlphaMissense predicts likely pathogenic (score 0.6633) — an in-silico prediction, not a clinical call.

CABP7 p.Gly49Ser

c.145G>A · VCV4217663

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6633 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0072%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6633	likely pathogenic
REVEL	0.753	pathogenic-leaning
SaProt	LLR -9.83	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 9,141 bp · p 0.0056 · regional, not allelic
Overall
CADD	32.0	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 0.0072% European (non-Finnish) · 85/1,179,956 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00552% 89/1,613,578 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0072%	13,882
East Asian	0.00668%	14,962
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Gly49Ser
Coding: c.145G>A
MANE Select: NM_182527
Type: single nucleotide variant
Location: chr22:29727697 (GRCh38)
Gene constraint: LOEUF 0.817 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 58.35 · 1 PDB
Residue 49: the ef-hand 1 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.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-gly49ser (accessed [today's date]).

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