Is DAAM2 p.Arg1061Gln (c.3182G>A) pathogenic?

DAAM2 p.Arg1061Gln (c.3182G>A) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-31). AlphaMissense: ambiguous (0.431); Ultra-rare (popmax 0.0294%, afr); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Arg1061Gln (c.3182G>A)?

DAAM2 p.Arg1061Gln (c.3182G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Arg1061Gln (c.3182G>A) in the general population?

DAAM2 p.Arg1061Gln (c.3182G>A) is ultra-rare (popmax 0.0294%, afr) (gnomAD).

What do computational predictors say about DAAM2 p.Arg1061Gln (c.3182G>A)?

AlphaMissense predicts ambiguous (score 0.431) — an in-silico prediction, not a clinical call.

DAAM2 p.Arg1061Gln

c.3182G>A · VCV4009168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.431 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0294%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.431	ambiguous
REVEL	0.667	pathogenic-leaning
SaProt	LLR -7.21	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	31.0	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 0.0294% African / African-American · 22/74,830 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0168%

Overall 0.0018% 29/1,609,784 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0294%	3,401
Admixed American	0.00503%	19,890
South Asian	0.00221%	45,344
European (non-Finnish)	0.00017%	588,599

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.Arg1061Gln
Coding: c.3182G>A
MANE Select: NM_001201427
Type: single nucleotide variant
Location: chr6:39902012 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 1061: 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

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

Similar variants

DAAM2 p.Arg1061Leu Uncertain significance ★ ⚠ same residue
DAAM2 p.Arg1061Trp Uncertain significance ★ ⚠ 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-arg1061gln (accessed [today's date]).

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