Is DAAM2 p.Arg1008Trp (c.3022C>T) pathogenic?

DAAM2 p.Arg1008Trp (c.3022C>T) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.269); Very rare (popmax 0.00271%, afr); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Arg1008Trp (c.3022C>T)?

DAAM2 p.Arg1008Trp (c.3022C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Arg1008Trp (c.3022C>T) in the general population?

DAAM2 p.Arg1008Trp (c.3022C>T) is very rare (popmax 0.00271%, afr) (gnomAD).

What do computational predictors say about DAAM2 p.Arg1008Trp (c.3022C>T)?

AlphaMissense predicts likely benign (score 0.269) — an in-silico prediction, not a clinical call.

DAAM2 p.Arg1008Trp

c.3022C>T · rs573237647 · VCV2313690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.269 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.269	likely benign
REVEL	0.512	indeterminate
SaProt	LLR -12.52	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.034, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	26.3	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 0.00271% African / African-American · 2/73,682 alleles

Filtering AF 0.00193% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00229% 36/1,569,234 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00271%	36,841
European (non-Finnish)	0.00269%	37,235
South Asian	0.00233%	42,919
Admixed American	0.00181%	55,232

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.Arg1008Trp
Coding: c.3022C>T
MANE Select: NM_001201427
dbSNP: rs573237647
Type: single nucleotide variant
Location: chr6:39901852 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 1008: 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

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DAAM2 p.Ile699Val Uncertain significance ★★ ⚠ same condition
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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-arg1008trp (accessed [today's date]).

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