Is DDHD2 p.Trp56Arg (c.166T>A) pathogenic?

DDHD2 p.Trp56Arg (c.166T>A) is classified Uncertain significance in DDHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1.

How common is DDHD2 p.Trp56Arg (c.166T>A) in the general population?

DDHD2 p.Trp56Arg (c.166T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDHD2 p.Trp56Arg (c.166T>A)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

DDHD2 p.Trp56Arg

c.166T>A · VCV3337019

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9995	likely pathogenic · top 1% in DDHD2
REVEL	0.704	pathogenic-leaning
SaProt	LLR -14.68	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 21 kb · p 0.01 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: DDHD2
Protein: p.Trp56Arg
Coding: c.166T>A
MANE Select: NM_015214
Type: single nucleotide variant
Location: chr8:38233160 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.70
Residue 56: the wwe domain

Full DDHD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDHD2 c.1126-2A>G Likely pathogenic ★★ same type
DDHD2 c.1248+2T>C Likely pathogenic ★★ same type
DDHD2 p.Arg232Ter Pathogenic ★★ same type
DDHD2 p.Arg329Ter Pathogenic ★★ same type
DDHD2 p.Arg422Ter Likely pathogenic ★★ same type
DDHD2 p.Arg516Ter Pathogenic ★★ same type
DDHD2 p.Asp660His Pathogenic/Likely pathogenic ★★ same type
DDHD2 p.Gln286Ter Pathogenic/Likely pathogenic ★★ 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/ddhd2-p-trp56arg (accessed [today's date]).

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