Is DHDH p.Val161Asp (c.482T>A) pathogenic?

DHDH p.Val161Asp (c.482T>A) is classified Uncertain significance in DHDH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-20). AlphaMissense: ambiguous (0.547); Very rare (popmax 0.00401%, afr).

How common is DHDH p.Val161Asp (c.482T>A) in the general population?

DHDH p.Val161Asp (c.482T>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DHDH p.Val161Asp (c.482T>A)?

AlphaMissense predicts ambiguous (score 0.547) — an in-silico prediction, not a clinical call.

DHDH p.Val161Asp

c.482T>A · rs753333350 · VCV2473110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.547 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.547	ambiguous
REVEL	0.195	benign-leaning
SaProt	LLR -7.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.9	phastCons 0.054
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.26 · regional, not allelic
Overall
CADD	15.85	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 0.00401% African / African-American · 3/74,786 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,612,824 alleles · very rare exomes 2/1,461,876 · genomes 2/150,948 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,929
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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: DHDH
Protein: p.Val161Asp
Coding: c.482T>A
MANE Select: NM_014475
dbSNP: rs753333350
Type: single nucleotide variant
Location: chr19:48939564 (GRCh38)
Gene constraint: LOEUF 1.275 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 98.19

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

Similar variants

DHDH p.Ala111Ser Uncertain significance ★ ⚠ same type
DHDH p.Ala134Thr Uncertain significance ★ ⚠ same type
DHDH p.Ala173Thr Uncertain significance ★ ⚠ same type
DHDH p.Ala70Ser Uncertain significance ★ ⚠ same type
DHDH p.Ala89Val Uncertain significance ★ ⚠ same type
DHDH p.Arg107His Uncertain significance ★ ⚠ same type
DHDH p.Arg107Ser Uncertain significance ★ ⚠ same type
DHDH p.Arg127His 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/dhdh-p-val161asp (accessed [today's date]).

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