Is DAAM2 p.Leu579= (c.1735C>T) pathogenic?

DAAM2 p.Leu579= (c.1735C>T) is classified Likely benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-23). Very rare (popmax 0.00223%, eas); Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Leu579= (c.1735C>T)?

DAAM2 p.Leu579= (c.1735C>T) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Leu579= (c.1735C>T) in the general population?

DAAM2 p.Leu579= (c.1735C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

DAAM2 p.Leu579=

c.1735C>T · rs2481856192 · VCV3050344

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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
Constraint at this position
Conservation	phyloP 0.039	GERP -4.9, phastCons 0.001
Overall
CADD	8.308	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,838 alleles

Overall 6.84e-05% 1/1,461,200 alleles · very rare

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.Leu579=
Coding: c.1735C>T
MANE Select: NM_001201427
dbSNP: rs2481856192
Type: single nucleotide variant
Location: chr6:39879367 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 579: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation); the fh1 domain; the 'disordered' region

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

Disease context

DAAM2-related disorder

Similar variants

DAAM2 p.Leu579Arg 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
DAAM2 c.2983-8G>C 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-leu579 (accessed [today's date]).

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