Is DUSP6 p.Ser144Ala (c.430T>G) pathogenic?

DUSP6 p.Ser144Ala (c.430T>G) is classified Benign in DUSP6 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0589); Common (popmax 38.5%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about DUSP6 p.Ser144Ala (c.430T>G)?

AlphaMissense predicts likely benign (score 0.0589) — an in-silico prediction, not a clinical call.

DUSP6 p.Ser144Ala

Q: How common is DUSP6 p.Ser144Ala (c.430T>G) in the general population?

DUSP6 p.Ser144Ala (c.430T>G) is common (popmax 38.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.430T>G · rs770087 · VCV1261506

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0589 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 38.5%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0589	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -7.21	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 2.4	GERP -2, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 1,392 bp · p 0.98 · regional, not allelic
Overall
CADD	21.3	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 38.5% African / African-American · 28,765/74,798 alleles

Filtering AF 38.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 37.9%

Overall 19.6% 314,958/1,605,312 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	38.5%	3
Amishnot grpmax-eligible	29.1%	3
Admixed American	23.6%	4
Remaining individualsnot grpmax-eligible	19.7%	5
European (non-Finnish)	19.3%	5
Ashkenazi Jewishnot grpmax-eligible	18.6%	5
South Asian	17.8%	6
Middle Eastern	17%	6
Finnishnot grpmax-eligible	15%	7
East Asian	3.17%	32

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: DUSP6
Protein: p.Ser144Ala
Coding: c.430T>G
MANE Select: NM_001946
dbSNP: rs770087
Type: single nucleotide variant
Location: chr12:89350996 (GRCh38)
Gene constraint: LOEUF 0.45 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 76.13 · 2 PDB
Residue 144: the rhodanese domain; a UniProt-annotated variant site (in)

Full DUSP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP6 p.Ala141Asp Uncertain significance ★★ ⚠ same type
DUSP6 p.Ala57Thr Uncertain significance ★★ ⚠ same type
DUSP6 p.Asp93Glu Uncertain significance ★★ ⚠ same type
DUSP6 p.Glu32Lys Uncertain significance ★★ ⚠ same type
DUSP6 p.Gly30Cys Uncertain significance ★★ ⚠ same type
DUSP6 p.Phe77Ile Uncertain significance ★★ ⚠ same type
DUSP6 c.400+231T>C Benign ★★ same type
DUSP6 c.401-113T>A Benign ★★ 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/dusp6-p-ser144ala (accessed [today's date]).

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