Is DOC2B p.Arg232Cys (c.694C>T) pathogenic?

DOC2B p.Arg232Cys (c.694C>T) is classified Uncertain significance in DOC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.9217); Absent from gnomAD v4.1.

How common is DOC2B p.Arg232Cys (c.694C>T) in the general population?

DOC2B p.Arg232Cys (c.694C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DOC2B p.Arg232Cys (c.694C>T)?

AlphaMissense predicts likely pathogenic (score 0.9217) — an in-silico prediction, not a clinical call.

DOC2B p.Arg232Cys

c.694C>T · VCV3841856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9217 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9217	likely pathogenic
REVEL	0.217	benign-leaning
SaProt	LLR -16.48	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	phastCons 0.99
Overall
CADD	23.8	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

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: DOC2B
Protein: p.Arg232Cys
Coding: c.694C>T
MANE Select: NM_003585
Type: single nucleotide variant
Location: chr17:161486 (GRCh38)
Gene constraint: LOEUF 1.371 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.21
Residue 232: the c2 1 domain

Full DOC2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DOC2B p.Ala103Thr Uncertain significance ★ ⚠ same type
DOC2B p.Ala295Thr Uncertain significance ★ ⚠ same type
DOC2B p.Ala54Glu Uncertain significance ★ ⚠ same type
DOC2B p.Ala58Ser Uncertain significance ★ ⚠ same type
DOC2B p.Ala63Thr Uncertain significance ★ ⚠ same type
DOC2B p.Arg186Cys Uncertain significance ★ same type
DOC2B p.Arg186His Uncertain significance ★ ⚠ same type
DOC2B p.Arg209His 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/doc2b-p-arg232cys (accessed [today's date]).

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