Is DDX51 p.Pro230Ser (c.688C>T) pathogenic?

DDX51 p.Pro230Ser (c.688C>T) is classified Uncertain significance in DDX51 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely benign (0.3285); Very rare (popmax 0.00333%, amr).

How common is DDX51 p.Pro230Ser (c.688C>T) in the general population?

DDX51 p.Pro230Ser (c.688C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about DDX51 p.Pro230Ser (c.688C>T)?

AlphaMissense predicts likely benign (score 0.3285) — an in-silico prediction, not a clinical call.

DDX51 p.Pro230Ser

c.688C>T · rs781637028 · VCV3081105

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3285 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3285	likely benign
REVEL	0.448	indeterminate
SaProt	LLR -11.28	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 5,021 bp · p 5.4e-07 · regional, not allelic
Overall
CADD	26.0	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 0.00333% Admixed American · 2/60,018 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000274% 4/1,460,040 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,009
South Asian	0.0011%	91,084
European (non-Finnish)	8.47e-05%	1,179,984

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.Pro230Ser
Coding: c.688C>T
MANE Select: NM_175066
dbSNP: rs781637028
Type: single nucleotide variant
Location: chr12:132142405 (GRCh38)
Gene constraint: LOEUF 1.265 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.64

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-pro230ser (accessed [today's date]).

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