Is DHDDS p.Ala316Thr (c.946G>A) pathogenic?

DHDDS p.Ala316Thr (c.946G>A) is classified Uncertain significance in DHDDS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-24). AlphaMissense: likely benign (0.1072); Ultra-rare (popmax 0.0167%, amr); Associated with Inborn genetic diseases.

What condition is associated with DHDDS p.Ala316Thr (c.946G>A)?

DHDDS p.Ala316Thr (c.946G>A) is associated with Inborn genetic diseases, retinitis pigmentosa 59 (ClinVar).

How common is DHDDS p.Ala316Thr (c.946G>A) in the general population?

DHDDS p.Ala316Thr (c.946G>A) is ultra-rare (popmax 0.0167%, amr) (gnomAD).

What do computational predictors say about DHDDS p.Ala316Thr (c.946G>A)?

AlphaMissense predicts likely benign (score 0.1072) — an in-silico prediction, not a clinical call.

DHDDS p.Ala316Thr

c.946G>A · rs760304376 · VCV2166029

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1072 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1072	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -10.24	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 26 kb · p 0.063 · regional, not allelic
Overall
CADD	23.3	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 0.0167% Admixed American · 10/60,012 alleles

Filtering AF 0.009% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00681%

Overall 0.00366% 59/1,613,430 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0167%	6,001
European (non-Finnish)	0.00407%	24,584
Remaining individualsnot grpmax-eligible	0.0016%	62,430

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: DHDDS
Protein: p.Ala316Thr
Coding: c.946G>A
MANE Select: NM_205861
dbSNP: rs760304376
Type: single nucleotide variant
Location: chr1:26469075 (GRCh38)
Gene constraint: LOEUF 0.536 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 95.01 · 9 PDB
Residue 316: a UniProt-annotated variant site (in rp59; in a patient with congenital disorder of glycosylation); an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa 59

Similar variants

DHDDS p.Ala316Ser Uncertain significance ★ ⚠ same residue
DHDDS c.658-2A>G Likely pathogenic ★★ same condition
DHDDS p.Arg205Gln Pathogenic ★★ same condition
DHDDS p.Arg211Gln Pathogenic ★★ same condition
DHDDS p.Arg37Cys Pathogenic ★★ same condition
DHDDS p.Arg37His Pathogenic/Likely pathogenic ★★ same condition
DHDDS p.Arg37Ser Pathogenic ★★ same condition
DHDDS p.Arg38His Pathogenic/Likely pathogenic ★★ same condition

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/dhdds-p-ala316thr (accessed [today's date]).

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