Is CAPN11 p.Phe697Val (c.2089T>G) pathogenic?

CAPN11 p.Phe697Val (c.2089T>G) is classified Uncertain significance in CAPN11 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: likely benign (0.2931); Ultra-rare (popmax 0.0192%, nfe).

How common is CAPN11 p.Phe697Val (c.2089T>G) in the general population?

CAPN11 p.Phe697Val (c.2089T>G) is ultra-rare (popmax 0.0192%, nfe) (gnomAD).

What do computational predictors say about CAPN11 p.Phe697Val (c.2089T>G)?

AlphaMissense predicts likely benign (score 0.2931) — an in-silico prediction, not a clinical call.

CAPN11 p.Phe697Val

c.2089T>G · rs200526960 · VCV2364899

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2931 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0192%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2931	likely benign
REVEL	0.514	indeterminate
SaProt	LLR -9.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 25 kb · p 0.17 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0192% European (non-Finnish) · 226/1,179,528 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0162%

Overall 0.0169% 273/1,613,562 alleles · ultra-rare exomes 239/1,461,286 · genomes 34/152,276 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0562%	1,778
European (non-Finnish)grpmax	0.0192%	5,219
Remaining individualsnot grpmax-eligible	0.0128%	7,806
African / African-American	0.00267%	37,508
Admixed American	0.00167%	60,014

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: CAPN11
Protein: p.Phe697Val
Coding: c.2089T>G
MANE Select: NM_007058
dbSNP: rs200526960
Type: single nucleotide variant
Location: chr6:44183190 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10
Residue 697: the 'domain iv' region

Full CAPN11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAPN11 p.Gln133Ter Likely benign ★★ same type
CAPN11 p.Ala29Pro Uncertain significance ★ ⚠ same type
CAPN11 p.Ala405Pro Uncertain significance ★ ⚠ same type
CAPN11 p.Ala405Thr Uncertain significance ★ ⚠ same type
CAPN11 p.Ala461Ser Uncertain significance ★ ⚠ same type
CAPN11 p.Ala472Thr Uncertain significance ★ ⚠ same type
CAPN11 p.Ala599Thr Uncertain significance ★ ⚠ same type
CAPN11 p.Ala689Glu 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/capn11-p-phe697val (accessed [today's date]).

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