Is DHDH p.Asn278Asp (c.832A>G) pathogenic?

DHDH p.Asn278Asp (c.832A>G) is classified Uncertain significance in DHDH (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). AlphaMissense: ambiguous (0.4297); Rare (popmax 1%, afr).

How common is DHDH p.Asn278Asp (c.832A>G) in the general population?

DHDH p.Asn278Asp (c.832A>G) is rare (popmax 1%, afr) (gnomAD).

What do computational predictors say about DHDH p.Asn278Asp (c.832A>G)?

AlphaMissense predicts ambiguous (score 0.4297) — an in-silico prediction, not a clinical call.

DHDH p.Asn278Asp

c.832A>G · VCV4659862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4297 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 1%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4297	ambiguous
REVEL	0.187	benign-leaning
SaProt	LLR -11.18	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.26 · regional, not allelic
Overall
CADD	18.5	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 1% African / African-American · 750/75,018 alleles

Filtering AF 0.94% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.917%

Overall 0.0518% 836/1,614,014 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1%	100
Admixed American	0.0784%	1,276
Remaining individualsnot grpmax-eligible	0.0496%	2,016
South Asian	0.0011%	91,080
European (non-Finnish)	0.000593%	168,564

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.Asn278Asp
Coding: c.832A>G
MANE Select: NM_014475
Type: single nucleotide variant
Location: chr19:48944444 (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-asn278asp (accessed [today's date]).

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