Is DDX4 p.Ala511Val (c.1532C>T) pathogenic?

DDX4 p.Ala511Val (c.1532C>T) is classified Uncertain significance in DDX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-27). AlphaMissense: ambiguous (0.5502); Very rare (popmax 8.48e-05%, nfe); Associated with male infertility.

What condition is associated with DDX4 p.Ala511Val (c.1532C>T)?

DDX4 p.Ala511Val (c.1532C>T) is associated with male infertility (ClinVar).

How common is DDX4 p.Ala511Val (c.1532C>T) in the general population?

DDX4 p.Ala511Val (c.1532C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about DDX4 p.Ala511Val (c.1532C>T)?

AlphaMissense predicts ambiguous (score 0.5502) — an in-silico prediction, not a clinical call.

DDX4 p.Ala511Val

c.1532C>T · rs2532837489 · VCV3024482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5502 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

male infertility

Computational evidence

Protein change
AlphaMissense	0.5502	ambiguous
REVEL	0.43	indeterminate
SaProt	LLR -10.51	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.51	unconstrained · MANE · 22 kb · p 2.5e-13 · regional, not allelic
Overall
CADD	25.5	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 8.48e-05% European (non-Finnish) · 1/1,179,374 alleles

Overall 6.2e-05% 1/1,612,864 alleles · very rare exomes 1/1,460,624 · genomes 0/152,240 · joint denominator

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: DDX4
Protein: p.Ala511Val
Coding: c.1532C>T
MANE Select: NM_024415
dbSNP: rs2532837489
Type: single nucleotide variant
Location: chr5:55798488 (GRCh38)
Gene constraint: LOEUF 0.34 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.06

Full DDX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

male infertility — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DDX4 c.1172+9A>G Benign ★★ same type
DDX4 p.Ala448= Benign ★★ same type
DDX4 p.Lys472Glu Benign ★★ same type
DDX4 p.Ala304Val Uncertain significance ★ ⚠ same type
DDX4 p.Ala385Val Uncertain significance ★ ⚠ same type
DDX4 p.Ala493Val Uncertain significance ★ ⚠ same type
DDX4 p.Arg111Lys Uncertain significance ★ ⚠ same type
DDX4 p.Arg123Trp 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/ddx4-p-ala511val (accessed [today's date]).

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