Is DUSP12 p.Glu139Val (c.416A>T) pathogenic?

DUSP12 p.Glu139Val (c.416A>T) is classified Uncertain significance in DUSP12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.221); Very rare (popmax 0.00401%, afr).

How common is DUSP12 p.Glu139Val (c.416A>T) in the general population?

DUSP12 p.Glu139Val (c.416A>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DUSP12 p.Glu139Val (c.416A>T)?

AlphaMissense predicts likely benign (score 0.221) — an in-silico prediction, not a clinical call.

DUSP12 p.Glu139Val

c.416A>T · VCV4662511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.221 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.221	likely benign
REVEL	0.529	indeterminate
SaProt	LLR -9.68	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 3.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 7,142 bp · p 0.25 · regional, not allelic
Overall
CADD	23.3	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 0.00401% African / African-American · 3/74,898 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0013% 21/1,613,572 alleles · very rare exomes 19/1,461,430 · genomes 2/152,142 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,966
European (non-Finnish)	0.00153%	65,548

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: DUSP12
Protein: p.Glu139Val
Coding: c.416A>T
MANE Select: NM_007240
Type: single nucleotide variant
Location: chr1:161751739 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.21 · 2 PDB
Residue 139: the tyrosine-protein phosphatase domain; an α-helix

Full DUSP12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP12 p.Ala167Val Uncertain significance ★ ⚠ same type
DUSP12 p.Arg20Ser Uncertain significance ★ ⚠ same type
DUSP12 p.Arg222Ser Uncertain significance ★ ⚠ same type
DUSP12 p.Arg238Cys Uncertain significance ★ ⚠ same type
DUSP12 p.Arg77His Uncertain significance ★ ⚠ same type
DUSP12 p.Asp9Asn Uncertain significance ★ ⚠ same type
DUSP12 p.Gln306Arg Uncertain significance ★ ⚠ same type
DUSP12 p.Glu107Val 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/dusp12-p-glu139val (accessed [today's date]).

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