Is DUSP10 p.Ala99Ser (c.295G>T) pathogenic?

DUSP10 p.Ala99Ser (c.295G>T) is classified Uncertain significance in DUSP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-06). AlphaMissense: likely benign (0.0709); Very rare (popmax 0.00915%, nfe).

How common is DUSP10 p.Ala99Ser (c.295G>T) in the general population?

DUSP10 p.Ala99Ser (c.295G>T) is very rare (popmax 0.00915%, nfe) (gnomAD).

What do computational predictors say about DUSP10 p.Ala99Ser (c.295G>T)?

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

DUSP10 p.Ala99Ser

c.295G>T · rs773122250 · VCV2521451

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

very rare (popmax 0.00915%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0709	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.30	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 -1.4	GERP -1.7
Regional constraint	o/e 0.89	unconstrained · MANE · 37 kb · p 0.0053 · regional, not allelic
Overall
CADD	1.895	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 0.00915% European (non-Finnish) · 108/1,180,048 alleles

Filtering AF 0.00774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00719%

Overall 0.00706% 114/1,614,024 alleles · very rare exomes 104/1,461,886 · genomes 10/152,138 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00915%	10,926
African / African-American	0.00401%	24,965
South Asian	0.0022%	45,538
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: DUSP10
Protein: p.Ala99Ser
Coding: c.295G>T
MANE Select: NM_007207
dbSNP: rs773122250
Type: single nucleotide variant
Location: chr1:221739450 (GRCh38)
Gene constraint: LOEUF 0.704 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 70.95 · 23 PDB

Full DUSP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP10 p.Ala197Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala300Thr Uncertain significance ★ ⚠ same type
DUSP10 p.Ala47Val Uncertain significance ★ ⚠ same type
DUSP10 p.Ala55Pro Uncertain significance ★ ⚠ same type
DUSP10 p.Arg203Gln Uncertain significance ★ ⚠ same type
DUSP10 p.Arg203Trp Uncertain significance ★ ⚠ same type
DUSP10 p.Arg245Leu Uncertain significance ★ same type
DUSP10 p.Arg345Gln 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/dusp10-p-ala99ser (accessed [today's date]).

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