Is CAPN11 p.Ile172Val (c.514A>G) pathogenic?

CAPN11 p.Ile172Val (c.514A>G) is classified Uncertain significance in CAPN11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1515); Absent from gnomAD v4.1.

How common is CAPN11 p.Ile172Val (c.514A>G) in the general population?

CAPN11 p.Ile172Val (c.514A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAPN11 p.Ile172Val (c.514A>G)?

AlphaMissense predicts likely benign (score 0.1515) — an in-silico prediction, not a clinical call.

CAPN11 p.Ile172Val

c.514A>G · rs2533677535 · VCV3137041

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,553,768)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.559	indeterminate
SaProt	LLR -8.24	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 2, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 25 kb · p 0.17 · regional, not allelic
Overall
CADD	24.3	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

No allele count reported in gnomAD v4.1 (AN 1,553,768). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAPN11
Protein: p.Ile172Val
Coding: c.514A>G
MANE Select: NM_007058
dbSNP: rs2533677535
Type: single nucleotide variant
Location: chr6:44172406 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10
Residue 172: the calpain catalytic domain

Full CAPN11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN11 p.Gln133Ter Likely benign ★★ same type
CAPN11 p.Ala29Pro Uncertain significance ★ ⚠ same type
CAPN11 p.Ala405Pro Uncertain significance ★ ⚠ same type
CAPN11 p.Ala405Thr Uncertain significance ★ ⚠ same type
CAPN11 p.Ala461Ser Uncertain significance ★ ⚠ same type
CAPN11 p.Ala472Thr Uncertain significance ★ ⚠ same type
CAPN11 p.Ala599Thr Uncertain significance ★ ⚠ same type
CAPN11 p.Ala689Glu 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/capn11-p-ile172val (accessed [today's date]).

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