Is CAP2 p.Glu328Gly (c.983A>G) pathogenic?

CAP2 p.Glu328Gly (c.983A>G) is classified Uncertain significance in CAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: ambiguous (0.4841); Very rare (popmax 8.48e-05%, nfe).

How common is CAP2 p.Glu328Gly (c.983A>G) in the general population?

CAP2 p.Glu328Gly (c.983A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CAP2 p.Glu328Gly (c.983A>G)?

AlphaMissense predicts ambiguous (score 0.4841) — an in-silico prediction, not a clinical call.

CAP2 p.Glu328Gly

c.983A>G · VCV3484693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4841 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4841	ambiguous
REVEL	0.594	indeterminate
SaProt	LLR -13.91	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Overall
CADD	29.2	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 8.48e-05% European (non-Finnish) · 1/1,179,616 alleles

Overall 6.84e-05% 1/1,461,120 alleles · very 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: CAP2
Protein: p.Glu328Gly
Coding: c.983A>G
MANE Select: NM_019894 · reported on NM_006366
Type: single nucleotide variant
Location: chr6:17541129 (GRCh38)
Structure: AlphaFold pLDDT 88.01
Residue 328: the peptidase s1 domain

Full CAP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAP2 p.Arg17His Uncertain significance ★★ ⚠ same type
CAP2 p.His203Arg Uncertain significance ★★ ⚠ same type
TMPRSS4 p.Ala44Val Likely benign ★★ same type
CAP2 c.1003-5T>G Uncertain significance ★ same type
CAP2 p.Ala162Thr Uncertain significance ★ ⚠ same type
CAP2 p.Ala262Pro Uncertain significance ★ ⚠ same type
CAP2 p.Ala272Thr Uncertain significance ★ ⚠ same type
CAP2 p.Ala294Thr 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/cap2-p-glu328gly (accessed [today's date]).

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