Is DAAM2 p.Ile828= (c.2484C>T) pathogenic?

DAAM2 p.Ile828= (c.2484C>T) is classified Benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-17). Common (popmax 59.6%, mid) — too common for a highly-penetrant pathogenic allele; Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Ile828= (c.2484C>T)?

DAAM2 p.Ile828= (c.2484C>T) is associated with DAAM2-related disorder (ClinVar).

DAAM2 p.Ile828=

Q: How common is DAAM2 p.Ile828= (c.2484C>T) in the general population?

DAAM2 p.Ile828= (c.2484C>T) is common (popmax 59.6%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2484C>T · rs3008815 · VCV3059968

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 59.6%, mid) — 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 -8.5	GERP -5.6
Overall
CADD	4.354	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 59.6% Middle Eastern · 3,603/6,044 alleles

Filtering AF 58.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 58.2%

Overall 51.6% 830,434/1,610,908 alleles · common exomes 756,249/1,458,966 · genomes 74,185/151,942 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	69.6%	1
Middle Easterngrpmax	59.6%	2
South Asian	58.8%	2
Ashkenazi Jewishnot grpmax-eligible	55.4%	2
European (non-Finnish)	52.1%	2
Remaining individualsnot grpmax-eligible	52.1%	2
Finnishnot grpmax-eligible	52%	2
Admixed American	50.5%	2
African / African-American	41.1%	2
East Asian	35.5%	3

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ile828=
Coding: c.2484C>T
MANE Select: NM_001201427
dbSNP: rs3008815
Type: single nucleotide variant
Location: chr6:39896954 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 828: 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-ile828 (accessed [today's date]).

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