Is DHDH p.Pro269Gln (c.806C>A) pathogenic?

DHDH p.Pro269Gln (c.806C>A) is classified Uncertain significance in DHDH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.1269); Very rare (popmax 0.00801%, afr).

How common is DHDH p.Pro269Gln (c.806C>A) in the general population?

DHDH p.Pro269Gln (c.806C>A) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about DHDH p.Pro269Gln (c.806C>A)?

AlphaMissense predicts likely benign (score 0.1269) — an in-silico prediction, not a clinical call.

DHDH p.Pro269Gln

c.806C>A · rs754384756 · VCV3082018

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1269	likely benign
REVEL	0.125	moderately benign-leaning
SaProt	LLR -11.36	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 2.4	phastCons 0.85
Regional constraint	o/e 0.95	unconstrained · MANE · 11 kb · p 0.26 · regional, not allelic
Overall
CADD	18.53	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 0.00801% African / African-American · 6/74,922 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000682% 11/1,614,012 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,487
Remaining individualsnot grpmax-eligible	0.0064%	15,620
South Asian	0.0011%	91,092

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.Pro269Gln
Coding: c.806C>A
MANE Select: NM_014475
dbSNP: rs754384756
Type: single nucleotide variant
Location: chr19:48944418 (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.Pro269Leu Likely benign ★ ⚠ same residue
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

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-pro269gln (accessed [today's date]).

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