Is DACH2 p.Gly85Val (c.254G>T) pathogenic?

DACH2 p.Gly85Val (c.254G>T) is classified Uncertain significance in DACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-26). AlphaMissense: likely pathogenic (0.9319); Absent from gnomAD v4.1.

How common is DACH2 p.Gly85Val (c.254G>T) in the general population?

DACH2 p.Gly85Val (c.254G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DACH2 p.Gly85Val (c.254G>T)?

AlphaMissense predicts likely pathogenic (score 0.9319) — an in-silico prediction, not a clinical call.

DACH2 p.Gly85Val

c.254G>T · VCV3838142

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9319 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9319	likely pathogenic
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -15.69	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.3	GERP 0.34, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 399 bp · p 0.15 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DACH2
Protein: p.Gly85Val
Coding: c.254G>T
MANE Select: NM_053281
Type: single nucleotide variant
Location: chrX:86148874 (GRCh38)
Structure: AlphaFold pLDDT 62.69
Residue 85: the 'dachbox-n' region

Full DACH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DACH2 p.Arg539His Uncertain significance ★★ ⚠ same type
DACH2 p.Ala219Val Conflicting classifications of pathogenicity ★ ⚠ same type
DACH2 p.Ala221Asp Uncertain significance ★ ⚠ same type
DACH2 p.Ala221Ser Uncertain significance ★ ⚠ same type
DACH2 p.Ala223Val Uncertain significance ★ ⚠ same type
DACH2 p.Ala285Glu Uncertain significance ★ ⚠ same type
DACH2 p.Ala296Val Uncertain significance ★ ⚠ same type
DACH2 p.Ala362Gly 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/dach2-p-gly85val (accessed [today's date]).

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