Is DACH2 p.Pro315= (c.945A>G) pathogenic?

DACH2 p.Pro315= (c.945A>G) is classified Likely benign in DACH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). Very rare (popmax 0.00225%, nfe).

How common is DACH2 p.Pro315= (c.945A>G) in the general population?

DACH2 p.Pro315= (c.945A>G) is very rare (popmax 0.00225%, nfe) (gnomAD).

DACH2 p.Pro315=

c.945A>G · rs766248312 · VCV2661010

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00225%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.33	GERP -4, phastCons 0.53
Overall
CADD	8.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% European (non-Finnish) · 20/889,328 alleles

Filtering AF 0.00147% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00119%

Overall 0.00175% 21/1,201,647 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00225%	44,466
Admixed American	0.0022%	45,505

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.Pro315=
Coding: c.945A>G
MANE Select: NM_053281
dbSNP: rs766248312
Type: single nucleotide variant
Location: chrX:86714561 (GRCh38)
Structure: AlphaFold pLDDT 62.69

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

Similar variants

DACH2 p.Pro315Thr 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-pro315 (accessed [today's date]).

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