Is DAAM1 p.Pro103Arg (c.308C>G) pathogenic?

DAAM1 p.Pro103Arg (c.308C>G) is classified Uncertain significance in DAAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely pathogenic (0.9973); Absent from gnomAD v4.1.

How common is DAAM1 p.Pro103Arg (c.308C>G) in the general population?

DAAM1 p.Pro103Arg (c.308C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAAM1 p.Pro103Arg (c.308C>G)?

AlphaMissense predicts likely pathogenic (score 0.9973) — an in-silico prediction, not a clinical call.

DAAM1 p.Pro103Arg

c.308C>G · VCV3270751

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9973 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9973	likely pathogenic · top 4% in DAAM1
REVEL	0.928	moderately pathogenic-leaning
SaProt	LLR -19.45	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 39 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	25.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAAM1
Protein: p.Pro103Arg
Coding: c.308C>G
MANE Select: NM_001270520
Type: single nucleotide variant
Location: chr14:59315314 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.52 · 2 PDB
Residue 103: the gbd/fh3 domain

Full DAAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAAM1 p.Arg1011Gly Uncertain significance ★★ same type
DAAM1 p.Phe752Leu Uncertain significance ★★ ⚠ same type
DAAM1 p.Asn865His Benign ★★ same type
DAAM1 p.Asp679= Likely benign ★★ same type
DAAM1 p.Leu804= Benign ★★ same type
DAAM1 p.Pro49= Benign ★★ same type
DAAM1 c.1969-1685T>C Uncertain significance ★ ⚠ same type
DAAM1 c.1969-1686T>G Uncertain significance ★ ⚠ same type

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/daam1-p-pro103arg (accessed [today's date]).

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