Is CAPN6 p.Tyr117= (c.351C>T) pathogenic?

CAPN6 p.Tyr117= (c.351C>T) is classified Benign in CAPN6 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-06-09). Common (popmax 26.4%, afr) — too common for a highly-penetrant pathogenic allele.

CAPN6 p.Tyr117=

Q: How common is CAPN6 p.Tyr117= (c.351C>T) in the general population?

CAPN6 p.Tyr117= (c.351C>T) is common (popmax 26.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.351C>T · rs17882737 · VCV1258216

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 26.4%, afr) — 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 3.6	GERP -0.076, phastCons 1
Overall
CADD	5.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.4% African / African-American · 15,042/57,023 alleles

Filtering AF 26% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.9%

Overall 1.82% 21,954/1,209,172 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	26.4%	4
Middle Eastern	2.85%	35
Admixed American	2.71%	37
Remaining individualsnot grpmax-eligible	2.57%	39
Ashkenazi Jewishnot grpmax-eligible	0.649%	154
European (non-Finnish)	0.45%	222
South Asian	0.185%	541
Finnishnot grpmax-eligible	0.109%	915
East Asian	0.00592%	16,881

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: CAPN6
Protein: p.Tyr117=
Coding: c.351C>T
MANE Select: NM_014289
dbSNP: rs17882737
Type: single nucleotide variant
Location: chrX:111253163 (GRCh38)
Structure: AlphaFold pLDDT 91.57
Residue 117: the calpain catalytic domain

Full CAPN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN6 c.1158+128A>T Benign ★★ same type
CAPN6 c.1743+105G>A Benign ★★ same type
CAPN6 c.297+86C>T Benign ★★ same type
CAPN6 c.699+25C>T Benign ★★ same type
CAPN6 c.700-159T>C Benign ★★ same type
CAPN6 p.Val277Leu Benign ★★ same type
CAPN6 p.Arg260Cys Uncertain significance ★ ⚠ same type
CAPN6 p.Arg341His 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/capn6-p-tyr117 (accessed [today's date]).

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