Is DAOA p.Ser31Arg (c.93C>A) pathogenic?

DAOA p.Ser31Arg (c.93C>A) is classified Uncertain significance in DAOA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: ambiguous (0.4008); Ultra-rare (popmax 0.0165%, mid).

How common is DAOA p.Ser31Arg (c.93C>A) in the general population?

DAOA p.Ser31Arg (c.93C>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DAOA p.Ser31Arg (c.93C>A)?

AlphaMissense predicts ambiguous (score 0.4008) — an in-silico prediction, not a clinical call.

DAOA p.Ser31Arg

c.93C>A · VCV3499648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4008 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4008	ambiguous
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.33	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 -4.4	GERP -3
Regional constraint	o/e 1.30	unconstrained · MANE · 24 kb · p 6.4e-05 · regional, not allelic
Overall
CADD	1.782	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000669%

Overall 0.000683% 11/1,610,480 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Admixed American	0.00501%	19,957
Remaining individualsnot grpmax-eligible	0.00321%	31,179
European (non-Finnish)	0.000424%	235,576

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.Ser31Arg
Coding: c.93C>A
MANE Select: NM_172370
Type: single nucleotide variant
Location: chr13:105467101 (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.Ser31Gly Uncertain significance ★ ⚠ same residue
DAOA p.Ser31Asn Likely benign ★ same residue
DAOA p.Arg75= Likely benign ★★ same type
DAOA p.Ala108Pro Uncertain significance ★ ⚠ 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

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-ser31arg (accessed [today's date]).

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