Is DUSP5 p.Ser5Leu (c.14C>T) pathogenic?

DUSP5 p.Ser5Leu (c.14C>T) is classified Uncertain significance in DUSP5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely pathogenic (0.7099); Very rare (popmax 0.00148%, afr).

How common is DUSP5 p.Ser5Leu (c.14C>T) in the general population?

DUSP5 p.Ser5Leu (c.14C>T) is very rare (popmax 0.00148%, afr) (gnomAD).

What do computational predictors say about DUSP5 p.Ser5Leu (c.14C>T)?

AlphaMissense predicts likely pathogenic (score 0.7099) — an in-silico prediction, not a clinical call.

DUSP5 p.Ser5Leu

c.14C>T · VCV4245592

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7099 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00148%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7099	likely pathogenic
REVEL	0.09	moderately benign-leaning
SaProt	LLR -3.50	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP -0.46, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 8,933 bp · p 6.1e-05 · regional, not allelic
Overall
CADD	26.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00148% African / African-American · 1/67,414 alleles

Filtering AF 0.000316% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000228%

Overall 0.000625% 9/1,440,274 alleles · very rare exomes 7/1,291,538 · genomes 2/148,736 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00148%	67,414
European (non-Finnish)	0.000734%	136,328

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: DUSP5
Protein: p.Ser5Leu
Coding: c.14C>T
MANE Select: NM_004419
Type: single nucleotide variant
Location: chr10:110498135 (GRCh38)
Gene constraint: LOEUF 1.069 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.76 · 1 PDB

Full DUSP5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP5 p.Asp291Asn Uncertain significance ★★ ⚠ same type
DUSP5 p.Ala55Ser Benign ★★ same type
DUSP5 p.Ala104Val Uncertain significance ★ ⚠ same type
DUSP5 p.Ala59Pro Uncertain significance ★ ⚠ same type
DUSP5 p.Arg121Leu Uncertain significance ★ ⚠ same type
DUSP5 p.Arg16Ser Uncertain significance ★ ⚠ same type
DUSP5 p.Arg213Gln Uncertain significance ★ ⚠ same type
DUSP5 p.Arg269Cys 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/dusp5-p-ser5leu (accessed [today's date]).

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