Is DUSP14 p.Leu165Val (c.493C>G) pathogenic?

DUSP14 p.Leu165Val (c.493C>G) is classified Uncertain significance in DUSP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-17). AlphaMissense: likely benign (0.1787); Very rare (popmax 8.47e-05%, nfe).

How common is DUSP14 p.Leu165Val (c.493C>G) in the general population?

DUSP14 p.Leu165Val (c.493C>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DUSP14 p.Leu165Val (c.493C>G)?

AlphaMissense predicts likely benign (score 0.1787) — an in-silico prediction, not a clinical call.

DUSP14 p.Leu165Val

c.493C>G · rs2547491380 · VCV2326598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1787	likely benign
REVEL	0.339	indeterminate
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.2, phastCons 1
Overall
CADD	24.3	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 8.47e-05% European (non-Finnish) · 1/1,180,032 alleles

Overall 6.84e-05% 1/1,461,522 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: DUSP14
Protein: p.Leu165Val
Coding: c.493C>G
MANE Select: NM_007026
dbSNP: rs2547491380
Type: single nucleotide variant
Location: chr17:37512765 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 89.31 · 1 PDB
Residue 165: the tyrosine-protein phosphatase domain; an α-helix

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-leu165val (accessed [today's date]).

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