Is CAPN7 p.Leu749Val (c.2245C>G) pathogenic?

CAPN7 p.Leu749Val (c.2245C>G) is classified Likely benign in CAPN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely benign (0.0487); Ultra-rare (popmax 0.0164%, mid).

How common is CAPN7 p.Leu749Val (c.2245C>G) in the general population?

CAPN7 p.Leu749Val (c.2245C>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CAPN7 p.Leu749Val (c.2245C>G)?

AlphaMissense predicts likely benign (score 0.0487) — an in-silico prediction, not a clinical call.

CAPN7 p.Leu749Val

c.2245C>G · rs148241217 · VCV2263656

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0487 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0487	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.9, phastCons 0.002
Regional constraint	o/e 0.88	unconstrained · MANE · 28 kb · p 0.0017 · regional, not allelic
Overall
CADD	0.734	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 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000744% 12/1,613,474 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Admixed American	0.00167%	59,988
Remaining individualsnot grpmax-eligible	0.0016%	62,458
European (non-Finnish)	0.000763%	131,068

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: CAPN7
Protein: p.Leu749Val
Coding: c.2245C>G
MANE Select: NM_014296
dbSNP: rs148241217
Type: single nucleotide variant
Location: chr3:15250971 (GRCh38)
Gene constraint: LOEUF 0.882 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.88 · 2 PDB
Residue 749: the 'domain n' region

Full CAPN7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN7 c.2073+1G>T Uncertain significance ★ same type
CAPN7 p.Ala10Asp Uncertain significance ★ ⚠ same type
CAPN7 p.Ala10Ser Uncertain significance ★ ⚠ same type
CAPN7 p.Ala149Val Uncertain significance ★ ⚠ same type
CAPN7 p.Ala29Val Uncertain significance ★ ⚠ same type
CAPN7 p.Ala37Thr Uncertain significance ★ ⚠ same type
CAPN7 p.Ala39Asp Uncertain significance ★ ⚠ same type
CAPN7 p.Ala459Ser 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/capn7-p-leu749val (accessed [today's date]).

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