Is DGKH p.Asp381Gly (c.1142A>G) pathogenic?

DGKH p.Asp381Gly (c.1142A>G) is classified Uncertain significance in DGKH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: likely benign (0.2029); Very rare (popmax 0.00381%, nfe).

How common is DGKH p.Asp381Gly (c.1142A>G) in the general population?

DGKH p.Asp381Gly (c.1142A>G) is very rare (popmax 0.00381%, nfe) (gnomAD).

What do computational predictors say about DGKH p.Asp381Gly (c.1142A>G)?

AlphaMissense predicts likely benign (score 0.2029) — an in-silico prediction, not a clinical call.

DGKH p.Asp381Gly

c.1142A>G · VCV4239887

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00381%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2029	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -11.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 60 kb · p 4.1e-11 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 0.00381% European (non-Finnish) · 45/1,179,990 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00297% 48/1,613,978 alleles · very rare exomes 46/1,461,768 · genomes 2/152,210 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00381%	26,222
Finnishnot grpmax-eligible	0.00312%	32,018
Remaining individualsnot grpmax-eligible	0.0016%	62,484

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DGKH
Protein: p.Asp381Gly
Coding: c.1142A>G
MANE Select: NM_178009
Type: single nucleotide variant
Location: chr13:42168463 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.33
Residue 381: the dagkc domain

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

Similar variants

DGKH p.Ala113Val Uncertain significance ★ ⚠ same type
DGKH p.Ala118Thr Uncertain significance ★ ⚠ same type
DGKH p.Ala19Ser Uncertain significance ★ ⚠ same type
DGKH p.Ala506Thr Uncertain significance ★ ⚠ same type
DGKH p.Ala627Thr Uncertain significance ★ ⚠ same type
DGKH p.Ala673Val Uncertain significance ★ ⚠ same type
DGKH p.Ala981Thr Uncertain significance ★ ⚠ same type
DGKH p.Ala985Thr 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/dgkh-p-asp381gly (accessed [today's date]).

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