Is DUSP12 p.Ala167Val (c.500C>T) pathogenic?

DUSP12 p.Ala167Val (c.500C>T) is classified Uncertain significance in DUSP12 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-08-17). AlphaMissense: likely benign (0.0912); Ultra-rare (popmax 0.096%, afr).

How common is DUSP12 p.Ala167Val (c.500C>T) in the general population?

DUSP12 p.Ala167Val (c.500C>T) is ultra-rare (popmax 0.096%, afr) (gnomAD).

What do computational predictors say about DUSP12 p.Ala167Val (c.500C>T)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

DUSP12 p.Ala167Val

c.500C>T · rs145422605 · VCV2375032

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.096%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 1.8, phastCons 0.99
Regional constraint	o/e 0.94	unconstrained · MANE · 7,142 bp · p 0.25 · regional, not allelic
Overall
CADD	19.59	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 0.096% African / African-American · 72/74,996 alleles

Filtering AF 0.0782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0716%

Overall 0.0049% 79/1,613,390 alleles · ultra-rare exomes 34/1,461,162 · genomes 45/152,228 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.096%	1,042
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.00334%	29,984

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.Ala167Val
Coding: c.500C>T
MANE Select: NM_007240
dbSNP: rs145422605
Type: single nucleotide variant
Location: chr1:161751907 (GRCh38)
Gene constraint: LOEUF 0.945 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.21 · 2 PDB
Residue 167: 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.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
DUSP12 p.Glu139Val 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-ala167val (accessed [today's date]).

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