Is DUSP14 p.Phe66Leu (c.198C>A) pathogenic?

DUSP14 p.Phe66Leu (c.198C>A) is classified Uncertain significance in DUSP14 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: likely pathogenic (0.8946); Rare (popmax 0.28%, amr).

How common is DUSP14 p.Phe66Leu (c.198C>A) in the general population?

DUSP14 p.Phe66Leu (c.198C>A) is rare (popmax 0.28%, amr) (gnomAD).

What do computational predictors say about DUSP14 p.Phe66Leu (c.198C>A)?

AlphaMissense predicts likely pathogenic (score 0.8946) — an in-silico prediction, not a clinical call.

DUSP14 p.Phe66Leu

c.198C>A · rs772044110 · VCV2235972

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8946 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.28%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8946	likely pathogenic
REVEL	0.202	benign-leaning
SaProt	LLR -5.37	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 6	GERP 1.3, phastCons 1
Overall
CADD	21.1	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 0.28% Admixed American · 168/60,006 alleles

Filtering AF 0.245% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.232%

Overall 0.0104% 168/1,614,114 alleles · rare exomes 59/1,461,894 · genomes 109/152,220 · joint denominator

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.Phe66Leu
Coding: c.198C>A
MANE Select: NM_007026
dbSNP: rs772044110
Type: single nucleotide variant
Location: chr17:37512470 (GRCh38)
Gene constraint: LOEUF 0.766 · pLI 0.50 (gnomAD)
Structure: AlphaFold pLDDT 89.31 · 1 PDB
Residue 66: the tyrosine-protein phosphatase domain

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-phe66leu (accessed [today's date]).

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