Is DDX49 p.Ile172Val (c.514A>G) pathogenic?

DDX49 p.Ile172Val (c.514A>G) is classified Uncertain significance in DDX49 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-07). AlphaMissense: likely benign (0.1107); Very rare (popmax 0.000593%, nfe).

How common is DDX49 p.Ile172Val (c.514A>G) in the general population?

DDX49 p.Ile172Val (c.514A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

What do computational predictors say about DDX49 p.Ile172Val (c.514A>G)?

AlphaMissense predicts likely benign (score 0.1107) — an in-silico prediction, not a clinical call.

DDX49 p.Ile172Val

c.514A>G · VCV3839110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1107 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000593%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1107	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 8,571 bp · p 0.15 · regional, not allelic
Overall
CADD	21.5	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 0.000593% European (non-Finnish) · 7/1,179,732 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.00048% 7/1,459,262 alleles · very 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: DDX49
Protein: p.Ile172Val
Coding: c.514A>G
MANE Select: NM_019070
Type: single nucleotide variant
Location: chr19:18922392 (GRCh38)
Gene constraint: LOEUF 1.194 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.72
Residue 172: the helicase atp-binding domain

Full DDX49 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DDX49 p.Ala132Val Uncertain significance ★ ⚠ same type
DDX49 p.Ala154Val Uncertain significance ★ ⚠ same type
DDX49 p.Ala174Glu Uncertain significance ★ ⚠ same type
DDX49 p.Ala174Val Uncertain significance ★ ⚠ same type
DDX49 p.Ala233Pro Uncertain significance ★ ⚠ same type
DDX49 p.Ala290Thr Uncertain significance ★ ⚠ same type
DDX49 p.Ala35Pro Uncertain significance ★ ⚠ same type
DDX49 p.Ala379Val 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/ddx49-p-ile172val (accessed [today's date]).

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