Is DUSP14 p.Ser169Leu (c.506C>T) pathogenic?

DUSP14 p.Ser169Leu (c.506C>T) is classified Uncertain significance in DUSP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-03). AlphaMissense: ambiguous (0.3508); Very rare (popmax 0.00933%, afr).

How common is DUSP14 p.Ser169Leu (c.506C>T) in the general population?

DUSP14 p.Ser169Leu (c.506C>T) is very rare (popmax 0.00933%, afr) (gnomAD).

What do computational predictors say about DUSP14 p.Ser169Leu (c.506C>T)?

AlphaMissense predicts ambiguous (score 0.3508) — an in-silico prediction, not a clinical call.

DUSP14 p.Ser169Leu

c.506C>T · VCV3505834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3508 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00933%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3508	ambiguous
REVEL	0.118	moderately benign-leaning
SaProt	LLR -12.19	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.2, phastCons 1
Overall
CADD	24.6	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 0.00933% African / African-American · 7/75,050 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.000868% 14/1,613,748 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00933%	10,721
South Asian	0.00329%	30,362
European (non-Finnish)	0.000339%	295,010

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.Ser169Leu
Coding: c.506C>T
MANE Select: NM_007026
Type: single nucleotide variant
Location: chr17:37512778 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 89.31 · 1 PDB

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-ser169leu (accessed [today's date]).

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