Is CAP1 p.Ser246Leu (c.737C>T) pathogenic?

CAP1 p.Ser246Leu (c.737C>T) is classified Uncertain significance in CAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). AlphaMissense: likely benign (0.1116); Absent from gnomAD v4.1.

How common is CAP1 p.Ser246Leu (c.737C>T) in the general population?

CAP1 p.Ser246Leu (c.737C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAP1 p.Ser246Leu (c.737C>T)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

CAP1 p.Ser246Leu

c.737C>T · VCV4218702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -7.68	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 4	GERP 2.3, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 12 kb · p 1.1e-11 · regional, not allelic
Overall
CADD	20.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAP1
Protein: p.Ser246Leu
Coding: c.737C>T
MANE Select: NM_006367
Type: single nucleotide variant
Location: chr1:40067646 (GRCh38)
Gene constraint: LOEUF 0.361 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 82.85 · 5 PDB

Full CAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CAP1 p.Ala73= Benign ★★ same type
CAP1 p.Tyr31= Benign ★★ same type
CAP1 p.Ala145Ser Uncertain significance ★ ⚠ same type
CAP1 p.Ala161Ser Uncertain significance ★ ⚠ same type
CAP1 p.Ala259Ser Uncertain significance ★ ⚠ same type
CAP1 p.Ala259Thr Uncertain significance ★ ⚠ same type
CAP1 p.Ala270Gly Uncertain significance ★ ⚠ same type
CAP1 p.Ala302Val 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/cap1-p-ser246leu (accessed [today's date]).

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