Is DAAM2 p.Cys383Phe (c.1148G>T) pathogenic?

DAAM2 p.Cys383Phe (c.1148G>T) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: ambiguous (0.5134); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Cys383Phe (c.1148G>T)?

DAAM2 p.Cys383Phe (c.1148G>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Cys383Phe (c.1148G>T) in the general population?

DAAM2 p.Cys383Phe (c.1148G>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DAAM2 p.Cys383Phe (c.1148G>T)?

AlphaMissense predicts ambiguous (score 0.5134) — an in-silico prediction, not a clinical call.

DAAM2 p.Cys383Phe

c.1148G>T · VCV4616921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5134 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5134	ambiguous
REVEL	0.774	moderately pathogenic-leaning
SaProt	LLR -7.62	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 5e-07 · regional, not allelic
Overall
CADD	28.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,176,584 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,457,442 alleles · very rare

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.Cys383Phe
Coding: c.1148G>T
MANE Select: NM_001201427
Type: single nucleotide variant
Location: chr6:39873341 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 383: the gbd/fh3 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

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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-cys383phe (accessed [today's date]).

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