Is CAPN2 p.Arg71Trp (c.211C>T) pathogenic?

CAPN2 p.Arg71Trp (c.211C>T) is classified Uncertain significance in CAPN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-06). AlphaMissense: likely benign (0.1515); Very rare (popmax 0.000695%, nfe).

How common is CAPN2 p.Arg71Trp (c.211C>T) in the general population?

CAPN2 p.Arg71Trp (c.211C>T) is very rare (popmax 0.000695%, nfe) (gnomAD).

What do computational predictors say about CAPN2 p.Arg71Trp (c.211C>T)?

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

CAPN2 p.Arg71Trp

c.211C>T · VCV4648143

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1515 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000695%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1515	likely benign
REVEL	0.564	indeterminate
SaProt	LLR -11.14	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP -0.079, phastCons 0.41
Regional constraint	o/e 0.88	unconstrained · MANE · 62 kb · p 0.00029 · regional, not allelic
Overall
CADD	27.4	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 0.000695% European (non-Finnish) · 8/1,151,694 alleles

Filtering AF 0.000299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000216%

Overall 0.000516% 8/1,551,496 alleles · very rare exomes 8/1,399,586 · genomes 0/151,910 · joint denominator

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: CAPN2
Protein: p.Arg71Trp
Coding: c.211C>T
MANE Select: NM_001748
Type: single nucleotide variant
Location: chr1:223712851 (GRCh38)
Gene constraint: LOEUF 1.026 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.48 · 3 PDB
Residue 71: the calpain catalytic domain

Full CAPN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN2 p.Ala248Thr Uncertain significance ★★ ⚠ same type
CAPN2 p.Gly72Asp Uncertain significance ★★ ⚠ same type
CAPN2 p.Asp48= Benign ★★ same type
CAPN2 p.Lys677Gln Benign ★★ same type
CAPN2 p.Ala101Pro Uncertain significance ★ ⚠ same type
CAPN2 p.Ala171Asp Uncertain significance ★ ⚠ same type
CAPN2 p.Ala194Ser Uncertain significance ★ ⚠ same type
CAPN2 p.Ala247Pro 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/capn2-p-arg71trp (accessed [today's date]).

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