Is DUSP28 p.Ala116Val (c.347C>T) pathogenic?

DUSP28 p.Ala116Val (c.347C>T) is classified Uncertain significance in DUSP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely pathogenic (0.8539); Very rare (popmax 0.000434%, nfe).

How common is DUSP28 p.Ala116Val (c.347C>T) in the general population?

DUSP28 p.Ala116Val (c.347C>T) is very rare (popmax 0.000434%, nfe) (gnomAD).

What do computational predictors say about DUSP28 p.Ala116Val (c.347C>T)?

AlphaMissense predicts likely pathogenic (score 0.8539) — an in-silico prediction, not a clinical call.

DUSP28 p.Ala116Val

c.347C>T · rs1444108607 · VCV2547639

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8539 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000434%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8539	likely pathogenic
REVEL	0.6	indeterminate
SaProt	LLR -14.04	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.1	GERP 1.3, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 779 bp · p 4.4e-10 · regional, not allelic
Overall
CADD	25.4	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

Grpmax group 0.000434% European (non-Finnish) · 5/1,151,508 alleles

Filtering AF 0.000127% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000326% 5/1,533,782 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: DUSP28
Protein: p.Ala116Val
Coding: c.347C>T
MANE Select: NM_001282771 · reported on NM_001370465
dbSNP: rs1444108607
Type: single nucleotide variant
Location: chr2:240561031 (GRCh38)

Full DUSP28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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/dusp28-p-ala116val (accessed [today's date]).

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