Is DUSP14 p.Ile180Val (c.538A>G) pathogenic?

DUSP14 p.Ile180Val (c.538A>G) is classified Uncertain significance in DUSP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.0709); Ultra-rare (popmax 0.0822%, mid).

How common is DUSP14 p.Ile180Val (c.538A>G) in the general population?

DUSP14 p.Ile180Val (c.538A>G) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

What do computational predictors say about DUSP14 p.Ile180Val (c.538A>G)?

AlphaMissense predicts likely benign (score 0.0709) — an in-silico prediction, not a clinical call.

DUSP14 p.Ile180Val

c.538A>G · rs377598867 · VCV2216044

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0709 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -5.04	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 -0.056	GERP -4.5, phastCons 0.002
Overall
CADD	3.171	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 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.0145% 234/1,613,216 alleles · ultra-rare exomes 209/1,461,018 · genomes 25/152,198 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
South Asian	0.0198%	5,060
European (non-Finnish)	0.017%	5,869
African / African-American	0.00534%	18,735
Admixed American	0.005%	20,002
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602
Remaining individualsnot grpmax-eligible	0.0032%	31,233

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.Ile180Val
Coding: c.538A>G
MANE Select: NM_007026
dbSNP: rs377598867
Type: single nucleotide variant
Location: chr17:37512810 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 89.31 · 1 PDB
Residue 180: 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-ile180val (accessed [today's date]).

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