Is DGKH p.Pro370Ala (c.1108C>G) pathogenic?

DGKH p.Pro370Ala (c.1108C>G) is classified Uncertain significance in DGKH (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-26). AlphaMissense: likely pathogenic (0.898); Rare (popmax 0.105%, sas).

How common is DGKH p.Pro370Ala (c.1108C>G) in the general population?

DGKH p.Pro370Ala (c.1108C>G) is rare (popmax 0.105%, sas) (gnomAD).

What do computational predictors say about DGKH p.Pro370Ala (c.1108C>G)?

AlphaMissense predicts likely pathogenic (score 0.898) — an in-silico prediction, not a clinical call.

DGKH p.Pro370Ala

c.1108C>G · rs766686422 · VCV2256960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.898 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.898	likely pathogenic
REVEL	0.537	indeterminate
SaProt	LLR -13.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.93 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6	GERP 1, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 60 kb · p 4.1e-11 · regional, not allelic
Overall
CADD	29.8	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

Grpmax group 0.105% South Asian · 91/86,638 alleles

Filtering AF 0.0875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0811%

Overall 0.00578% 92/1,592,532 alleles · rare exomes 90/1,440,570 · genomes 2/151,962 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.105%	952
Remaining individualsnot grpmax-eligible	0.00162%	61,570

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.Pro370Ala
Coding: c.1108C>G
MANE Select: NM_178009
dbSNP: rs766686422
Type: single nucleotide variant
Location: chr13:42166664 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.33
Residue 370: the dagkc domain

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

Similar variants

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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-pro370ala (accessed [today's date]).

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