Is DIAPH2 p.Arg262Lys (c.785G>A) pathogenic?

DIAPH2 p.Arg262Lys (c.785G>A) is classified Uncertain significance in DIAPH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). AlphaMissense: likely benign (0.1348); Absent from gnomAD v4.1.

How common is DIAPH2 p.Arg262Lys (c.785G>A) in the general population?

DIAPH2 p.Arg262Lys (c.785G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DIAPH2 p.Arg262Lys (c.785G>A)?

AlphaMissense predicts likely benign (score 0.1348) — an in-silico prediction, not a clinical call.

DIAPH2 p.Arg262Lys

c.785G>A · VCV3839950

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1348 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1348	likely benign
REVEL	0.574	indeterminate
SaProt	LLR -6.74	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 9.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 35 kb · p 2.5e-06 · regional, not allelic
Overall
CADD	22.9	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: DIAPH2
Protein: p.Arg262Lys
Coding: c.785G>A
MANE Select: NM_006729
Type: single nucleotide variant
Location: chrX:96916490 (GRCh38)
Structure: AlphaFold pLDDT 76.09
Residue 262: the gbd/fh3 domain

Full DIAPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DIAPH2 p.Ala83Thr Benign/Likely benign ★★ same type
DIAPH2 p.Ile475= Likely benign ★★ same type
DIAPH2 p.Phe504= Benign ★★ same type
DIAPH2 c.733-1G>T Uncertain significance ★ same type
DIAPH2 p.Ala125Val Uncertain significance ★ ⚠ same type
DIAPH2 p.Ala488Val Uncertain significance ★ ⚠ same type
DIAPH2 p.Ala672Thr Uncertain significance ★ ⚠ same type
DIAPH2 p.Ala6Thr 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/diaph2-p-arg262lys (accessed [today's date]).

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