Is DDHD2 p.Lys642Glu (c.1924A>G) pathogenic?

DDHD2 p.Lys642Glu (c.1924A>G) is classified Uncertain significance in DDHD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2014-09-10). AlphaMissense: likely benign (0.0744); Absent from gnomAD v4.1.

How common is DDHD2 p.Lys642Glu (c.1924A>G) in the general population?

DDHD2 p.Lys642Glu (c.1924A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DDHD2 p.Lys642Glu (c.1924A>G)?

AlphaMissense predicts likely benign (score 0.0744) — an in-silico prediction, not a clinical call.

DDHD2 p.Lys642Glu

c.1924A>G · rs77715495 · VCV210839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0744 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0744	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -5.27	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 5.4	GERP 1.3, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 6,537 bp · p 8.8e-05 · regional, not allelic
Overall
CADD	15.2	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: DDHD2
Protein: p.Lys642Glu
Coding: c.1924A>G
MANE Select: NM_015214
dbSNP: rs77715495
Type: single nucleotide variant
Location: chr8:38253588 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.70
Residue 642: a UniProt-annotated variant site (in spg54; likely pathogenic; loss of triacylglycerol hydrolase activity); the ddhd 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-lys642glu (accessed [today's date]).

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