Is DUSP16 p.Ala73Val (c.218C>T) pathogenic?

DUSP16 p.Ala73Val (c.218C>T) is classified Uncertain significance in DUSP16 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: ambiguous (0.4846); Ultra-rare (popmax 0.0111%, eas).

How common is DUSP16 p.Ala73Val (c.218C>T) in the general population?

DUSP16 p.Ala73Val (c.218C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about DUSP16 p.Ala73Val (c.218C>T)?

AlphaMissense predicts ambiguous (score 0.4846) — an in-silico prediction, not a clinical call.

DUSP16 p.Ala73Val

c.218C>T · rs746432264 · VCV2290808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4846 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4846	ambiguous
REVEL	0.182	moderately benign-leaning
SaProt	LLR -9.71	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 44 kb · p 0.0011 · regional, not allelic
Overall
CADD	24.3	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 0.0111% East Asian · 5/44,896 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000434% 7/1,614,008 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,979
European (non-Finnish)	0.000169%	589,998

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: DUSP16
Protein: p.Ala73Val
Coding: c.218C>T
MANE Select: NM_030640
dbSNP: rs746432264
Type: single nucleotide variant
Location: chr12:12520881 (GRCh38)
Gene constraint: LOEUF 0.502 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 60.81 · 3 PDB
Residue 73: the rhodanese domain

Full DUSP16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DUSP16 p.Ala2Thr Uncertain significance ★ ⚠ same type
DUSP16 p.Ala358Thr Uncertain significance ★ ⚠ same type
DUSP16 p.Arg130His Uncertain significance ★ ⚠ same type
DUSP16 p.Arg14Lys Uncertain significance ★ ⚠ same type
DUSP16 p.Arg208His Uncertain significance ★ ⚠ same type
DUSP16 p.Arg483Gln Uncertain significance ★ ⚠ same type
DUSP16 p.Arg598Cys Uncertain significance ★ ⚠ same type
DUSP16 p.Arg611Gln 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/dusp16-p-ala73val (accessed [today's date]).

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