Is CAPN10 p.Pro320Leu (c.959C>T) pathogenic?

CAPN10 p.Pro320Leu (c.959C>T) is classified Likely benign in CAPN10 (ClinVar, Single submitter, 3 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.2469); Rare (popmax 0.306%, nfe).

How common is CAPN10 p.Pro320Leu (c.959C>T) in the general population?

CAPN10 p.Pro320Leu (c.959C>T) is rare (popmax 0.306%, nfe) (gnomAD).

What do computational predictors say about CAPN10 p.Pro320Leu (c.959C>T)?

AlphaMissense predicts likely benign (score 0.2469) — an in-silico prediction, not a clinical call.

CAPN10 p.Pro320Leu

c.959C>T · rs140681762 · VCV730256

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.2469 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.306%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2469	likely benign
REVEL	0.466	indeterminate
SaProt	LLR -7.66	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.8	GERP 0.15, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 12 kb · p 0.013 · regional, not allelic
Overall
CADD	23.4	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 0.306% European (non-Finnish) · 3,612/1,179,986 alleles

Filtering AF 0.298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.294%

Overall 0.241% 3,892/1,613,734 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.306%	327
Finnishnot grpmax-eligible	0.215%	465
Remaining individualsnot grpmax-eligible	0.147%	679
African / African-American	0.0506%	1,975
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
Admixed American	0.00666%	15,005
South Asian	0.00549%	18,214
East Asian	0.00223%	44,866

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: CAPN10
Protein: p.Pro320Leu
Coding: c.959C>T
MANE Select: NM_023083
dbSNP: rs140681762
Type: single nucleotide variant
Location: chr2:240594671 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 320: the calpain catalytic domain

Full CAPN10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN10 p.Pro320= Uncertain significance same residue
CAPN10 p.Arg127Cys Uncertain significance ★★ ⚠ same type
CAPN10 p.Gly526Ser Uncertain significance ★★ ⚠ same type
CAPN10 p.Pro46Ser Uncertain significance ★★ ⚠ same type
CAPN10 p.Thr339Met Uncertain significance ★★ ⚠ same type
CAPN10 p.Ala477= Benign ★★ same type
CAPN10 p.Ala477Thr Benign ★★ same type
CAPN10 p.Arg555Cys Likely benign ★★ 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/capn10-p-pro320leu (accessed [today's date]).

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