Is DAAM2 p.Ile660= (c.1980C>A) pathogenic?

DAAM2 p.Ile660= (c.1980C>A) is classified Benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-04). Common (popmax 24%, afr) — too common for a highly-penetrant pathogenic allele; Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Ile660= (c.1980C>A)?

DAAM2 p.Ile660= (c.1980C>A) is associated with DAAM2-related disorder (ClinVar).

DAAM2 p.Ile660=

Q: How common is DAAM2 p.Ile660= (c.1980C>A) in the general population?

DAAM2 p.Ile660= (c.1980C>A) is common (popmax 24%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1980C>A · rs35383047 · VCV3060515

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 24%, afr) — 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 2.2	GERP 0.56, phastCons 1
Overall
CADD	12.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24% African / African-American · 17,954/74,932 alleles

Filtering AF 23.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 23.5%

Overall 6.59% 106,266/1,612,754 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	24%	4
East Asian	15.1%	7
South Asian	9.6%	10
Ashkenazi Jewishnot grpmax-eligible	9.06%	11
Admixed American	8.79%	11
Finnishnot grpmax-eligible	8.7%	11
Remaining individualsnot grpmax-eligible	7.86%	13
Middle Eastern	5.66%	18
European (non-Finnish)	4.58%	22
Amishnot grpmax-eligible	4.17%	24

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.Ile660=
Coding: c.1980C>A
MANE Select: NM_001201427
dbSNP: rs35383047
Type: single nucleotide variant
Location: chr6:39887512 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 660: 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

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-ile660 (accessed [today's date]).

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