Is DUSP14 p.Ile56Val (c.166A>G) pathogenic?

DUSP14 p.Ile56Val (c.166A>G) is classified Uncertain significance in DUSP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.1198); Ultra-rare (popmax 0.0117%, amr).

How common is DUSP14 p.Ile56Val (c.166A>G) in the general population?

DUSP14 p.Ile56Val (c.166A>G) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about DUSP14 p.Ile56Val (c.166A>G)?

AlphaMissense predicts likely benign (score 0.1198) — an in-silico prediction, not a clinical call.

DUSP14 p.Ile56Val

c.166A>G · rs200161175 · VCV2358224

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1198 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1198	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -7.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.1, phastCons 1
Overall
CADD	15.77	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 0.0117% Admixed American · 7/60,020 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.000743% 12/1,614,168 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,574
East Asian	0.00446%	22,436
Remaining individualsnot grpmax-eligible	0.0016%	62,510
African / African-American	0.00133%	75,040
South Asian	0.0011%	91,080

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: DUSP14
Protein: p.Ile56Val
Coding: c.166A>G
MANE Select: NM_007026
dbSNP: rs200161175
Type: single nucleotide variant
Location: chr17:37512438 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 89.31 · 1 PDB
Residue 56: the tyrosine-protein phosphatase domain; a β-strand

Full DUSP14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP14 p.Arg117Gly Uncertain significance ★ ⚠ same type
DUSP14 p.Arg163His Uncertain significance ★ ⚠ same type
DUSP14 p.Arg190Gln Uncertain significance ★ ⚠ same type
DUSP14 p.Arg45Gln Uncertain significance ★ ⚠ same type
DUSP14 p.Arg4Ser Uncertain significance ★ ⚠ same type
DUSP14 p.Asn44Ser Uncertain significance ★ ⚠ same type
DUSP14 p.Asn67Ser Uncertain significance ★ ⚠ same type
DUSP14 p.Asp183Asn 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/dusp14-p-ile56val (accessed [today's date]).

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