Is DAAM2 p.Arg597His (c.1790G>A) pathogenic?

DAAM2 p.Arg597His (c.1790G>A) is classified Benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-06). AlphaMissense: likely benign (0.0758); Rare (popmax 0.696%, eas); Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Arg597His (c.1790G>A)?

DAAM2 p.Arg597His (c.1790G>A) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Arg597His (c.1790G>A) in the general population?

DAAM2 p.Arg597His (c.1790G>A) is rare (popmax 0.696%, eas) (gnomAD).

What do computational predictors say about DAAM2 p.Arg597His (c.1790G>A)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

DAAM2 p.Arg597His

c.1790G>A · rs181701991 · VCV3034820

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.696%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DAAM2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.081	moderately benign-leaning
SaProt	LLR -5.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -4.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	23.8	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 0.696% East Asian · 312/44,842 alleles

Filtering AF 0.632% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.607%

Overall 0.0547% 882/1,613,808 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.696%	144
South Asian	0.205%	487
Remaining individualsnot grpmax-eligible	0.0864%	1,157
Admixed American	0.08%	1,250
Middle Eastern	0.066%	1,516
European (non-Finnish)	0.0225%	4,436
African / African-American	0.0147%	6,815

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.Arg597His
Coding: c.1790G>A
MANE Select: NM_001201427
dbSNP: rs181701991
Type: single nucleotide variant
Location: chr6:39879422 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 597: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation); the fh2 domain

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

Disease context

DAAM2-related disorder

Similar variants

DAAM2 p.Arg597Pro Uncertain significance ★ ⚠ same residue
DAAM2 p.Arg597Cys Likely benign ★ same residue
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

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-arg597his (accessed [today's date]).

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