Is DACH2 p.Ser397Asn (c.1190G>A) pathogenic?

DACH2 p.Ser397Asn (c.1190G>A) is classified Uncertain significance in DACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-20). AlphaMissense: ambiguous (0.5425); Very rare (popmax 0.00299%, eas).

How common is DACH2 p.Ser397Asn (c.1190G>A) in the general population?

DACH2 p.Ser397Asn (c.1190G>A) is very rare (popmax 0.00299%, eas) (gnomAD).

What do computational predictors say about DACH2 p.Ser397Asn (c.1190G>A)?

AlphaMissense predicts ambiguous (score 0.5425) — an in-silico prediction, not a clinical call.

DACH2 p.Ser397Asn

c.1190G>A · rs1479731868 · VCV3079924

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5425 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00299%, eas)

Computational evidence

Protein change
AlphaMissense	0.5425	ambiguous
REVEL	0.409	indeterminate
SaProt	LLR -7.71	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.9, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 455 kb · p 0.12 · regional, not allelic
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 0.00299% East Asian · 1/33,437 alleles

Overall 9.16e-05% 1/1,092,191 alleles · very rare

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: DACH2
Protein: p.Ser397Asn
Coding: c.1190G>A
MANE Select: NM_053281
dbSNP: rs1479731868
Type: single nucleotide variant
Location: chrX:86739832 (GRCh38)
Structure: AlphaFold pLDDT 62.69
Residue 397: the 'disordered' 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-ser397asn (accessed [today's date]).

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