Is DUS4L p.Pro247Gln (c.740C>A) pathogenic?

DUS4L p.Pro247Gln (c.740C>A) is classified Uncertain significance in DUS4L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-25). AlphaMissense: likely pathogenic (0.9927); Absent from gnomAD v4.1.

How common is DUS4L p.Pro247Gln (c.740C>A) in the general population?

DUS4L p.Pro247Gln (c.740C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DUS4L p.Pro247Gln (c.740C>A)?

AlphaMissense predicts likely pathogenic (score 0.9927) — an in-silico prediction, not a clinical call.

DUS4L p.Pro247Gln

c.740C>A · VCV4245456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9927 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9927	likely pathogenic · top 3% in DUS4L
REVEL	0.917	moderately pathogenic-leaning
SaProt	LLR -12.99	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.3 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DUS4L
Protein: p.Pro247Gln
Coding: c.740C>A
MANE Select: NM_181581
Type: single nucleotide variant
Location: chr7:107577346 (GRCh38)
Gene constraint: LOEUF 1.178 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.36

Full DUS4L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COG5 c.-292C>G Uncertain significance ★ same type
COG5 c.-367C>G Uncertain significance ★ same type
COG5 c.-56G>A Uncertain significance ★ same type
DUS4L p.Ala62Thr Uncertain significance ★ ⚠ same type
DUS4L p.Ala70Pro Uncertain significance ★ ⚠ same type
DUS4L p.Arg230Trp Uncertain significance ★ ⚠ same type
DUS4L p.Cys277Gly Uncertain significance ★ ⚠ same type
DUS4L p.Gln118Arg 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/dus4l-p-pro247gln (accessed [today's date]).

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