Is DAAM2 p.Arg597Pro (c.1790G>C) pathogenic?

DAAM2 p.Arg597Pro (c.1790G>C) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-07-13). AlphaMissense: likely benign (0.1566); Rare (popmax 0.791%, afr); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Arg597Pro (c.1790G>C)?

DAAM2 p.Arg597Pro (c.1790G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Arg597Pro (c.1790G>C) in the general population?

DAAM2 p.Arg597Pro (c.1790G>C) is rare (popmax 0.791%, afr) (gnomAD).

What do computational predictors say about DAAM2 p.Arg597Pro (c.1790G>C)?

AlphaMissense predicts likely benign (score 0.1566) — an in-silico prediction, not a clinical call.

DAAM2 p.Arg597Pro

c.1790G>C · rs181701991 · VCV2399325

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1566 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.791%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1566	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.48	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	20.9	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 0.791% African / African-American · 593/74,970 alleles

Filtering AF 0.738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.717%

Overall 0.0465% 750/1,613,810 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.791%	126
Middle Eastern	0.181%	551
Admixed American	0.08%	1,250
Remaining individualsnot grpmax-eligible	0.0784%	1,275
South Asian	0.00439%	22,771
European (non-Finnish)	0.00381%	26,219

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.Arg597Pro
Coding: c.1790G>C
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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DAAM2 p.Arg597Cys Likely benign ★ same residue
DAAM2 p.Arg597His Benign same residue
DAAM2 p.Arg335Trp Uncertain significance ★★ ⚠ same condition
DAAM2 p.Arg676Trp Uncertain significance ★★ ⚠ same condition
DAAM2 p.Arg990Cys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Gln760Arg Uncertain significance ★★ ⚠ same condition
DAAM2 p.Glu956Lys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Ile699Val Uncertain significance ★★ ⚠ 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-arg597pro (accessed [today's date]).

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