Is DAAM2 p.Lys982fs (c.2945_2957del) pathogenic?

DAAM2 p.Lys982fs (c.29452957del) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-22). Very rare (popmax 8.48e-05%, nfe); Associated with nephrotic syndrome, type 24.

What condition is associated with DAAM2 p.Lys982fs (c.2945_2957del)?

DAAM2 p.Lys982fs (c.2945_2957del) is associated with nephrotic syndrome, type 24 (ClinVar).

How common is DAAM2 p.Lys982fs (c.2945_2957del) in the general population?

DAAM2 p.Lys982fs (c.2945_2957del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

DAAM2 p.Lys982fs

c.2945_2957del · VCV4078454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

nephrotic syndrome, type 24

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (24 of 25, 48 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP 1.4, phastCons 1
Region caveats
Repeat context	tandem	(GAG)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,690 alleles

Overall 6.2e-05% 1/1,612,708 alleles · very rare exomes 1/1,461,142 · genomes 0/151,566 · joint denominator

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.Lys982fs
Coding: c.2945_2957del
MANE Select: NM_001201427
Type: Deletion
Location: chr6:39901424 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 982: 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

nephrotic syndrome, type 24 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DAAM2 p.Lys982Glu Uncertain significance ★ ⚠ same residue
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.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-lys982fs (accessed [today's date]).

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