Is DAAM2 p.Pro91Leu (c.272C>T) pathogenic?

DAAM2 p.Pro91Leu (c.272C>T) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-12-01). AlphaMissense: ambiguous (0.4965); Very rare (popmax 0.00178%, nfe).

How common is DAAM2 p.Pro91Leu (c.272C>T) in the general population?

DAAM2 p.Pro91Leu (c.272C>T) is very rare (popmax 0.00178%, nfe) (gnomAD).

What do computational predictors say about DAAM2 p.Pro91Leu (c.272C>T)?

AlphaMissense predicts ambiguous (score 0.4965) — an in-silico prediction, not a clinical call.

DAAM2 p.Pro91Leu

c.272C>T · rs1582695874 · VCV809929

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4965 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00178%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4965	ambiguous
REVEL	0.629	indeterminate
SaProt	LLR -6.90	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 8,771 bp · p 0.57 · regional, not allelic
Overall
CADD	28.2	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 0.00178% European (non-Finnish) · 21/1,179,750 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00144% 21/1,460,638 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.Pro91Leu
Coding: c.272C>T
MANE Select: NM_001201427
dbSNP: rs1582695874
Type: single nucleotide variant
Location: chr6:39864446 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 91: the gbd/fh3 domain

Full DAAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAAM2 p.Arg335Trp Uncertain significance ★★ ⚠ same type
DAAM2 p.Arg676Trp Uncertain significance ★★ ⚠ same type
DAAM2 p.Arg990Cys Uncertain significance ★★ ⚠ same type
DAAM2 p.Gln760Arg Uncertain significance ★★ ⚠ same type
DAAM2 p.Glu956Lys Uncertain significance ★★ ⚠ same type
DAAM2 p.Ile699Val Uncertain significance ★★ ⚠ same type
DAAM2 p.Pro74Thr Uncertain significance ★★ ⚠ same type
MOCS1 c.*1909A>G Likely benign ★★ 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/daam2-p-pro91leu (accessed [today's date]).

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