Is DAAM2 p.Arg1049Pro (c.3146G>C) pathogenic?

DAAM2 p.Arg1049Pro (c.3146G>C) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-10). AlphaMissense: likely pathogenic (0.6689); Very rare (popmax 0.00446%, eas); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Arg1049Pro (c.3146G>C)?

DAAM2 p.Arg1049Pro (c.3146G>C) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Arg1049Pro (c.3146G>C) in the general population?

DAAM2 p.Arg1049Pro (c.3146G>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about DAAM2 p.Arg1049Pro (c.3146G>C)?

AlphaMissense predicts likely pathogenic (score 0.6689) — an in-silico prediction, not a clinical call.

DAAM2 p.Arg1049Pro

c.3146G>C · rs200618513 · VCV3079869

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6689	likely pathogenic
REVEL	0.716	pathogenic-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	28.8	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 0.00446% East Asian · 2/44,800 alleles

Filtering AF 0.00074% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000277%

Overall 0.000479% 7/1,459,856 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,400
European (non-Finnish)	0.000424%	235,696

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.Arg1049Pro
Coding: c.3146G>C
MANE Select: NM_001201427
dbSNP: rs200618513
Type: single nucleotide variant
Location: chr6:39901976 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 1049: 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.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
DAAM2 p.Ala117Val Uncertain significance ★ ⚠ same condition
DAAM2 p.Ala167Thr 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-arg1049pro (accessed [today's date]).

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