Is CAPN10 p.Phe237= (c.711C>T) pathogenic?

CAPN10 p.Phe237= (c.711C>T) is classified Benign in CAPN10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-01-19). Common (popmax 5.53%, nfe) — too common for a highly-penetrant pathogenic allele.

CAPN10 p.Phe237=

Q: How common is CAPN10 p.Phe237= (c.711C>T) in the general population?

CAPN10 p.Phe237= (c.711C>T) is common (popmax 5.53%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.711C>T · rs13007017 · VCV1287585

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.53%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.89	GERP -2.2, phastCons 0.009
Overall
CADD	2.282	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.53% European (non-Finnish) · 64,892/1,173,770 alleles

Filtering AF 5.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.48%

Overall 4.81% 77,156/1,605,250 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	9.03%	11
European (non-Finnish)grpmax	5.53%	18
Amishnot grpmax-eligible	5.15%	19
Remaining individualsnot grpmax-eligible	4.27%	23
Ashkenazi Jewishnot grpmax-eligible	3.48%	29
Admixed American	2.25%	44
African / African-American	0.912%	110
South Asian	0.814%	123
Middle Eastern	0.697%	143
East Asian	0.00224%	44,586

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe237=
Coding: c.711C>T
MANE Select: NM_023083
dbSNP: rs13007017
Type: single nucleotide variant
Location: chr2:240593928 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.91
Residue 237: the calpain catalytic domain

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

Similar variants

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
CAPN10 p.Glu276= Benign/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-phe237 (accessed [today's date]).

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