Is CAP2 p.Leu52Pro (c.155T>C) pathogenic?

CAP2 p.Leu52Pro (c.155T>C) is classified Uncertain significance in CAP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-19). AlphaMissense: likely pathogenic (0.9598); Absent from gnomAD v4.1.

How common is CAP2 p.Leu52Pro (c.155T>C) in the general population?

CAP2 p.Leu52Pro (c.155T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAP2 p.Leu52Pro (c.155T>C)?

AlphaMissense predicts likely pathogenic (score 0.9598) — an in-silico prediction, not a clinical call.

CAP2 p.Leu52Pro

c.155T>C · rs2480828265 · VCV2443481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9598 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9598	likely pathogenic · top 1% in CAP2
REVEL	0.254	benign-leaning
SaProt	LLR -15.61	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.4, phastCons 1
Overall
CADD	27.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAP2
Protein: p.Leu52Pro
Coding: c.155T>C
MANE Select: NM_019894 · reported on NM_006366
dbSNP: rs2480828265
Type: single nucleotide variant
Location: chr6:17426623 (GRCh38)
Structure: AlphaFold pLDDT 88.01

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

Similar variants

TMPRSS4 p.Leu52Phe Uncertain significance ★ ⚠ same residue
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

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-leu52pro (accessed [today's date]).

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