Is CAPN15 p.Arg800Trp (c.2398C>T) pathogenic?

CAPN15 p.Arg800Trp (c.2398C>T) is classified Pathogenic in CAPN15 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-05-07). AlphaMissense: likely pathogenic (0.8834); Very rare (popmax 0.00323%, nfe); Associated with oculogastrointestinal-neurodevelopmental syndrome.

What condition is associated with CAPN15 p.Arg800Trp (c.2398C>T)?

CAPN15 p.Arg800Trp (c.2398C>T) is associated with oculogastrointestinal-neurodevelopmental syndrome (ClinVar).

How common is CAPN15 p.Arg800Trp (c.2398C>T) in the general population?

CAPN15 p.Arg800Trp (c.2398C>T) is very rare (popmax 0.00323%, nfe) (gnomAD).

What do computational predictors say about CAPN15 p.Arg800Trp (c.2398C>T)?

AlphaMissense predicts likely pathogenic (score 0.8834) — an in-silico prediction, not a clinical call.

CAPN15 p.Arg800Trp

c.2398C>T · rs762523863 · VCV1074291

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00323%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

oculogastrointestinal-neurodevelopmental syndrome

Computational evidence

Protein change
AlphaMissense	0.8834	likely pathogenic ✓ concordant with ClinVar
REVEL	0.401	indeterminate
SaProt	LLR -12.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP 0.29, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 4,055 bp · p 0.036 · regional, not allelic
Overall
CADD	24.4	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 0.00323% European (non-Finnish) · 37/1,146,906 alleles

Filtering AF 0.00238% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00208%

Overall 0.00265% 41/1,548,960 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00699%	14,313
European (non-Finnish)grpmax	0.00323%	30,997
Finnishnot grpmax-eligible	0.00171%	58,512
African / African-American	0.00137%	72,990

Ashkenazi Jewish 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: CAPN15
Protein: p.Arg800Trp
Coding: c.2398C>T
MANE Select: NM_005632
dbSNP: rs762523863
Type: single nucleotide variant
Location: chr16:552103 (GRCh38)
Gene constraint: LOEUF 0.974 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.65
Residue 800: a UniProt-annotated variant site (in ogin; uncertain significance)

Full CAPN15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

oculogastrointestinal-neurodevelopmental syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAPN15 p.Arg800Gln Uncertain significance ★ ⚠ same residue
CAPN15 p.Arg867Cys Uncertain significance ★★ ⚠ same condition
CAPN15 p.Cys363Arg Uncertain significance ★★ ⚠ same condition
CAPN15 p.Glu776Ala Uncertain significance ★★ ⚠ same condition
CAPN15 p.Val841Met Uncertain significance ★★ ⚠ same condition
CAPN15 p.Glu210Ter Likely pathogenic ★ same condition
CAPN15 p.Gly653Ser Likely pathogenic ★ same condition
CAPN15 p.Arg446Trp Uncertain significance ★ ⚠ same condition

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/capn15-p-arg800trp (accessed [today's date]).

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