Is DAAM2 p.Arg1059= (c.3177G>T) pathogenic?

DAAM2 p.Arg1059= (c.3177G>T) is classified Benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-05-01). Low-frequency (popmax 3.85%, afr); Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Arg1059= (c.3177G>T)?

DAAM2 p.Arg1059= (c.3177G>T) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Arg1059= (c.3177G>T) in the general population?

DAAM2 p.Arg1059= (c.3177G>T) is low-frequency (popmax 3.85%, afr) (gnomAD).

DAAM2 p.Arg1059=

c.3177G>T · rs115009770 · VCV3037540

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 3.85%, afr)

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
Pangolin	Δ0.43	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -0.041	GERP -1.1, phastCons 0.43
Overall
CADD	6.644	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.85% African / African-American · 2,886/74,970 alleles

Filtering AF 3.73% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.68%

Overall 0.25% 4,021/1,610,620 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.85%	26
Ashkenazi Jewishnot grpmax-eligible	0.722%	138
Remaining individualsnot grpmax-eligible	0.377%	265
Admixed American	0.367%	273
Middle Eastern	0.264%	378
European (non-Finnish)	0.0375%	2,664
South Asian	0.00771%	12,974
Finnishnot grpmax-eligible	0.00469%	21,316

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.Arg1059=
Coding: c.3177G>T
MANE Select: NM_001201427
dbSNP: rs115009770
Type: single nucleotide variant
Location: chr6:39902007 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 1059: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation)

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

Disease context

DAAM2-related disorder

Similar variants

DAAM2 p.Arg1059Gln Uncertain significance ★ ⚠ same residue
DAAM2 p.Arg1059Trp Uncertain significance ★ ⚠ 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-arg1059 (accessed [today's date]).

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