Is DAAM2 p.Met978Thr (c.2933T>C) pathogenic?

DAAM2 p.Met978Thr (c.2933T>C) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely benign (0.3087); Ultra-rare (popmax 0.0548%, afr); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Met978Thr (c.2933T>C)?

DAAM2 p.Met978Thr (c.2933T>C) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Met978Thr (c.2933T>C) in the general population?

DAAM2 p.Met978Thr (c.2933T>C) is ultra-rare (popmax 0.0548%, afr) (gnomAD).

What do computational predictors say about DAAM2 p.Met978Thr (c.2933T>C)?

AlphaMissense predicts likely benign (score 0.3087) — an in-silico prediction, not a clinical call.

DAAM2 p.Met978Thr

c.2933T>C · VCV3499487

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3087 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0548%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3087	likely benign
REVEL	0.226	benign-leaning
SaProt	LLR -8.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	23.2	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 0.0548% African / African-American · 41/74,772 alleles

Filtering AF 0.0415% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00316% 51/1,612,710 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0548%	1,824
Admixed American	0.00667%	14,988
Remaining individualsnot grpmax-eligible	0.0048%	20,823
South Asian	0.0011%	91,016
European (non-Finnish)	0.00017%	589,845

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.Met978Thr
Coding: c.2933T>C
MANE Select: NM_001201427
Type: single nucleotide variant
Location: chr6:39901423 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 978: 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

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-met978thr (accessed [today's date]).

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