Is DAAM2 p.Ser7Asn (c.20G>A) pathogenic?

DAAM2 p.Ser7Asn (c.20G>A) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-25). AlphaMissense: likely benign (0.0794); Ultra-rare (popmax 0.0171%, mid); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Ser7Asn (c.20G>A)?

DAAM2 p.Ser7Asn (c.20G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Ser7Asn (c.20G>A) in the general population?

DAAM2 p.Ser7Asn (c.20G>A) is ultra-rare (popmax 0.0171%, mid) (gnomAD).

What do computational predictors say about DAAM2 p.Ser7Asn (c.20G>A)?

AlphaMissense predicts likely benign (score 0.0794) — an in-silico prediction, not a clinical call.

DAAM2 p.Ser7Asn

c.20G>A · rs527543903 · VCV3079860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0794 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0171%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0794	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -7.05	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 2.2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 8,771 bp · p 0.57 · regional, not allelic
Overall
CADD	19.65	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 0.0171% Middle Eastern · 1/5,854 alleles

Filtering AF 0.00206% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00181%

Overall 0.0024% 37/1,543,144 alleles · ultra-rare exomes 35/1,390,808 · genomes 2/152,336 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0171%	5,854
Admixed American	0.00396%	25,223
European (non-Finnish)	0.00288%	34,696
South Asian	0.00124%	80,590

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.Ser7Asn
Coding: c.20G>A
MANE Select: NM_001201427
dbSNP: rs527543903
Type: single nucleotide variant
Location: chr6:39856322 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02

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.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
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-ser7asn (accessed [today's date]).

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