Is DDX25 p.Ser91Cys (c.272C>G) pathogenic?

DDX25 p.Ser91Cys (c.272C>G) is classified Uncertain significance in DDX25 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). AlphaMissense: likely benign (0.1758); Ultra-rare (popmax 0.0122%, eas).

How common is DDX25 p.Ser91Cys (c.272C>G) in the general population?

DDX25 p.Ser91Cys (c.272C>G) is ultra-rare (popmax 0.0122%, eas) (gnomAD).

What do computational predictors say about DDX25 p.Ser91Cys (c.272C>G)?

AlphaMissense predicts likely benign (score 0.1758) — an in-silico prediction, not a clinical call.

DDX25 p.Ser91Cys

c.272C>G · rs1281523273 · VCV2537360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1758 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0122%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1758	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -10.38	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 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.48 · regional, not allelic
Overall
CADD	28.8	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 0.0122% East Asian · 5/40,886 alleles

Filtering AF 0.00479% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.000322% 5/1,550,524 alleles · ultra-rare

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: DDX25
Protein: p.Ser91Cys
Coding: c.272C>G
MANE Select: NM_013264
dbSNP: rs1281523273
Type: single nucleotide variant
Location: chr11:125906170 (GRCh38)
Gene constraint: LOEUF 1.348 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.15 · 1 PDB

Full DDX25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PUS3 c.-47+3170T>C Pathogenic ★★ ⚠ same type
DDX25 c.1202-69C>T Benign ★★ same type
DDX25 c.1390+242C>T Benign ★★ same type
DDX25 c.1391-299T>C Benign ★★ same type
DDX25 c.311+155G>C Benign ★★ same type
DDX25 c.404+36T>C Benign ★★ same type
DDX25 c.507+53T>A Benign ★★ same type
DDX25 c.507+55G>T Benign ★★ 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/ddx25-p-ser91cys (accessed [today's date]).

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