Is DAOA p.Ala108Pro (c.322G>C) pathogenic?

DAOA p.Ala108Pro (c.322G>C) is classified Uncertain significance in DAOA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-28). AlphaMissense: ambiguous (0.5629); Very rare (popmax 0.00334%, amr).

How common is DAOA p.Ala108Pro (c.322G>C) in the general population?

DAOA p.Ala108Pro (c.322G>C) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about DAOA p.Ala108Pro (c.322G>C)?

AlphaMissense predicts ambiguous (score 0.5629) — an in-silico prediction, not a clinical call.

DAOA p.Ala108Pro

c.322G>C · VCV3838232

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5629 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5629	ambiguous
REVEL	0.224	benign-leaning
SaProt	LLR -6.53	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -1
Regional constraint	o/e 1.30	unconstrained · MANE · 24 kb · p 6.4e-05 · regional, not allelic
Overall
CADD	14.71	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 0.00334% Admixed American · 2/59,938 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00248% 40/1,613,682 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,969
European (non-Finnish)	0.00314%	31,889
Remaining individualsnot grpmax-eligible	0.0016%	62,462

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: DAOA
Protein: p.Ala108Pro
Coding: c.322G>C
MANE Select: NM_172370
Type: single nucleotide variant
Location: chr13:105489941 (GRCh38)
Gene constraint: LOEUF 1.457 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 46.78

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

Similar variants

DAOA p.Arg75= Likely benign ★★ same type
DAOA p.Arg122His Uncertain significance ★ ⚠ same type
DAOA p.Arg128Gly Uncertain significance ★ ⚠ same type
DAOA p.Glu94Asp Uncertain significance ★ ⚠ same type
DAOA p.His76Arg Uncertain significance ★ ⚠ same type
DAOA p.Ile44Val Uncertain significance ★ ⚠ same type
DAOA p.Leu126Val Uncertain significance ★ ⚠ same type
DAOA p.Met72Ile 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/daoa-p-ala108pro (accessed [today's date]).

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