Is DAAM2 p.Gln760Arg (c.2279A>G) pathogenic?

DAAM2 p.Gln760Arg (c.2279A>G) is classified Uncertain significance in DAAM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-20). AlphaMissense: likely benign (0.2525); Rare (popmax 0.105%, eas); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Gln760Arg (c.2279A>G)?

DAAM2 p.Gln760Arg (c.2279A>G) is associated with Inborn genetic diseases, nephrotic syndrome, type 24 (ClinVar).

How common is DAAM2 p.Gln760Arg (c.2279A>G) in the general population?

DAAM2 p.Gln760Arg (c.2279A>G) is rare (popmax 0.105%, eas) (gnomAD).

What do computational predictors say about DAAM2 p.Gln760Arg (c.2279A>G)?

AlphaMissense predicts likely benign (score 0.2525) — an in-silico prediction, not a clinical call.

DAAM2 p.Gln760Arg

c.2279A>G · rs570413956 · VCV2582484

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2525 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.105%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2525	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% East Asian · 47/44,826 alleles

Filtering AF 0.0809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0726%

Overall 0.00323% 52/1,611,696 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.105%	954
South Asian	0.00332%	30,139
European (non-Finnish)	0.00017%	589,459

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.Gln760Arg
Coding: c.2279A>G
MANE Select: NM_001201427
dbSNP: rs570413956
Type: single nucleotide variant
Location: chr6:39891660 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 760: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation); the fh2 domain

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

Also linked: nephrotic syndrome, type 24

Similar variants

DAAM2 p.Arg335Trp Uncertain significance ★★ ⚠ same condition
DAAM2 p.Arg676Trp Uncertain significance ★★ ⚠ same condition
DAAM2 p.Arg990Cys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Glu956Lys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Ile699Val Uncertain significance ★★ ⚠ same condition
DAAM2 p.Pro74Thr Uncertain significance ★★ ⚠ same condition
DAAM2 p.Arg66Ter Likely pathogenic ★ same condition
DAAM2 p.Gly1020Ter Likely pathogenic ★ 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-gln760arg (accessed [today's date]).

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