Is DAAM2 p.His9= (c.27T>C) pathogenic?

DAAM2 p.His9= (c.27T>C) is classified Benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-19). Common (popmax 7.35%, eas) — too common for a highly-penetrant pathogenic allele; Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.His9= (c.27T>C)?

DAAM2 p.His9= (c.27T>C) is associated with DAAM2-related disorder (ClinVar).

DAAM2 p.His9=

Q: How common is DAAM2 p.His9= (c.27T>C) in the general population?

DAAM2 p.His9= (c.27T>C) is common (popmax 7.35%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.27T>C · rs11965120 · VCV3060337

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 7.35%, eas) — too common for a highly-penetrant pathogenic allele

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 1.9	GERP 1.2, phastCons 1
Overall
CADD	8.479	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.35% East Asian · 2,945/40,078 alleles

Filtering AF 7.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.04%

Overall 1.4% 21,651/1,548,998 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	7.35%	14
Middle Eastern	4.24%	24
Remaining individualsnot grpmax-eligible	1.45%	69
European (non-Finnish)	1.35%	74
Admixed American	1.13%	88
Ashkenazi Jewishnot grpmax-eligible	0.784%	128
South Asian	0.711%	141
African / African-American	0.55%	182
Finnishnot grpmax-eligible	0.516%	194

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.His9=
Coding: c.27T>C
MANE Select: NM_001201427
dbSNP: rs11965120
Type: single nucleotide variant
Location: chr6:39856329 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02

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-his9 (accessed [today's date]).

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