Is DDX51 p.Ala403Ser (c.1207G>T) pathogenic?

DDX51 p.Ala403Ser (c.1207G>T) is classified Uncertain significance in DDX51 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-12-28). AlphaMissense: likely benign (0.0763); Rare (popmax 0.115%, mid).

How common is DDX51 p.Ala403Ser (c.1207G>T) in the general population?

DDX51 p.Ala403Ser (c.1207G>T) is rare (popmax 0.115%, mid) (gnomAD).

What do computational predictors say about DDX51 p.Ala403Ser (c.1207G>T)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

DDX51 p.Ala403Ser

c.1207G>T · rs200793638 · VCV2353810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.14	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 -0.53	GERP -2.2
Regional constraint	o/e 1.17	unconstrained · MANE · 5,021 bp · p 5.4e-07 · regional, not allelic
Overall
CADD	0.37	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 0.115% Middle Eastern · 7/6,074 alleles

Filtering AF 0.0541% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.0327% 523/1,598,686 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.115%	868
European (non-Finnish)	0.037%	2,705
South Asian	0.0352%	2,843
Finnishnot grpmax-eligible	0.0344%	2,910
Remaining individualsnot grpmax-eligible	0.0321%	3,118
Admixed American	0.01%	9,990
African / African-American	0.00667%	14,984

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: DDX51
Protein: p.Ala403Ser
Coding: c.1207G>T
MANE Select: NM_175066
dbSNP: rs200793638
Type: single nucleotide variant
Location: chr12:132141318 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.64
Residue 403: the helicase atp-binding domain

Full DDX51 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX51 p.Gly542= Likely benign ★★ same type
DDX51 p.Ala107Ser Uncertain significance ★ ⚠ same type
DDX51 p.Ala119Val Uncertain significance ★ ⚠ same type
DDX51 p.Ala141Thr Uncertain significance ★ ⚠ same type
DDX51 p.Ala144Thr Uncertain significance ★ ⚠ same type
DDX51 p.Ala183Pro Uncertain significance ★ ⚠ same type
DDX51 p.Ala237Pro Uncertain significance ★ ⚠ same type
DDX51 p.Ala25Thr 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/ddx51-p-ala403ser (accessed [today's date]).

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