Is DGKH p.Pro161Ser (c.481C>T) pathogenic?

DGKH p.Pro161Ser (c.481C>T) is classified Uncertain significance in DGKH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-20). AlphaMissense: likely benign (0.0829); Ultra-rare (popmax 0.033%, mid).

How common is DGKH p.Pro161Ser (c.481C>T) in the general population?

DGKH p.Pro161Ser (c.481C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about DGKH p.Pro161Ser (c.481C>T)?

AlphaMissense predicts likely benign (score 0.0829) — an in-silico prediction, not a clinical call.

DGKH p.Pro161Ser

c.481C>T · VCV4011164

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0829 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0829	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -5.57	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 0.86	GERP -3.7, phastCons 0.29
Regional constraint	o/e 0.71	unconstrained · MANE · 60 kb · p 4.1e-11 · regional, not allelic
Overall
CADD	9.027	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

Grpmax group 0.033% Middle Eastern · 2/6,064 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000621% 10/1,609,010 alleles · ultra-rare exomes 7/1,456,856 · genomes 3/152,154 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,032
African / African-American	0.00268%	37,280
South Asian	0.00112%	89,638
European (non-Finnish)	0.000424%	235,733

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.Pro161Ser
Coding: c.481C>T
MANE Select: NM_178009
Type: single nucleotide variant
Location: chr13:42155387 (GRCh38)
Gene constraint: LOEUF 0.689 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.33

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-pro161ser (accessed [today's date]).

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