Is DACH2 p.Ala5Ser (c.13G>T) pathogenic?

DACH2 p.Ala5Ser (c.13G>T) is classified Uncertain significance in DACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-18). AlphaMissense: likely benign (0.0902); Very rare (popmax 0.000915%, nfe).

How common is DACH2 p.Ala5Ser (c.13G>T) in the general population?

DACH2 p.Ala5Ser (c.13G>T) is very rare (popmax 0.000915%, nfe) (gnomAD).

What do computational predictors say about DACH2 p.Ala5Ser (c.13G>T)?

AlphaMissense predicts likely benign (score 0.0902) — an in-silico prediction, not a clinical call.

DACH2 p.Ala5Ser

c.13G>T · VCV4009222

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0902 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000915%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0902	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -5.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.2	GERP -0.36, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 399 bp · p 0.15 · regional, not allelic
Overall
CADD	16.07	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.000915% European (non-Finnish) · 8/874,529 alleles

Filtering AF 0.000393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000284%

Overall 0.000685% 8/1,168,211 alleles · very rare exomes 7/1,057,237 · genomes 1/110,974 · 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: DACH2
Protein: p.Ala5Ser
Coding: c.13G>T
MANE Select: NM_053281
Type: single nucleotide variant
Location: chrX:86148633 (GRCh38)
Structure: AlphaFold pLDDT 62.69

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

Similar variants

DACH2 p.Ala5Val Uncertain significance ★ ⚠ same residue
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

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-ala5ser (accessed [today's date]).

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