Is DAAM2 p.Thr123= (c.369G>T) pathogenic?

DAAM2 p.Thr123= (c.369G>T) is classified Likely benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-25). Very rare (popmax 0.00337%, amr); Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Thr123= (c.369G>T)?

DAAM2 p.Thr123= (c.369G>T) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Thr123= (c.369G>T) in the general population?

DAAM2 p.Thr123= (c.369G>T) is very rare (popmax 0.00337%, amr) (gnomAD).

DAAM2 p.Thr123=

c.369G>T · VCV3355881

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00337%, amr)

Conditions

DAAM2-related disorder

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 -5.9	GERP -4.1
Overall
CADD	0.429	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00337% Admixed American · 2/59,300 alleles

Filtering AF 0.00154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.0018% 29/1,607,708 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00337%	29,650
European (non-Finnish)	0.00221%	45,287
Remaining individualsnot grpmax-eligible	0.00161%	62,294

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: DAAM2
Protein: p.Thr123=
Coding: c.369G>T
MANE Select: NM_001201427
Type: single nucleotide variant
Location: chr6:39865015 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 123: the gbd/fh3 domain

Full DAAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DAAM2-related disorder

Similar variants

DAAM2 p.Ala829Thr Uncertain significance ⚠ same condition
DAAM2 p.Glu997Lys Uncertain significance same condition
DAAM2 p.Gly527Val Uncertain significance ⚠ same condition
DAAM2 c.1845+7A>G Likely benign same condition
DAAM2 c.2342-10C>T Likely benign same condition
DAAM2 c.2983-4G>A Likely benign same condition
DAAM2 c.2983-8G>C Likely benign same condition
DAAM2 p.Ala1054Thr Likely benign same condition

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/daam2-p-thr123 (accessed [today's date]).

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