Is DAAM2 p.Pro556= (c.1668A>C) pathogenic?

DAAM2 p.Pro556= (c.1668A>C) is classified Likely benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-09-18). Common (popmax 9.93%, amr) — too common for a highly-penetrant pathogenic allele; Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Pro556= (c.1668A>C)?

DAAM2 p.Pro556= (c.1668A>C) is associated with DAAM2-related disorder (ClinVar).

DAAM2 p.Pro556=

Q: How common is DAAM2 p.Pro556= (c.1668A>C) in the general population?

DAAM2 p.Pro556= (c.1668A>C) is common (popmax 9.93%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1668A>C · rs775891415 · VCV3040680

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 9.93%, amr) — too common for a highly-penetrant pathogenic allele

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 -5.4	GERP -3.8
Overall
CADD	0.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.93% Admixed American · 1,743/17,554 alleles

Filtering AF 9.54% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.38%

Overall 3.19% 17,447/547,080 alleles · common exomes 15,183/509,146 · genomes 2,264/37,934 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	9.93%	10
East Asian	8.68%	12
South Asian	8.16%	12
African / African-American	5.23%	19
Ashkenazi Jewishnot grpmax-eligible	5.15%	19
Remaining individualsnot grpmax-eligible	3.79%	26
Finnishnot grpmax-eligible	2.62%	38
European (non-Finnish)	2.2%	45
Middle Eastern	1.77%	56
Amishnot grpmax-eligible	1.23%	81

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.Pro556=
Coding: c.1668A>C
MANE Select: NM_001201427
dbSNP: rs775891415
Type: single nucleotide variant
Location: chr6:39879300 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 556: 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.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
DAAM2 p.Ala1054Thr 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-pro556 (accessed [today's date]).

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