Is AOC1 p.Pro305Ser (c.913C>T) pathogenic?

AOC1 p.Pro305Ser (c.913C>T) is classified Uncertain significance in AOC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-20). AlphaMissense: likely benign (0.1145); Ultra-rare (popmax 0.01%, amr).

How common is AOC1 p.Pro305Ser (c.913C>T) in the general population?

AOC1 p.Pro305Ser (c.913C>T) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about AOC1 p.Pro305Ser (c.913C>T)?

AlphaMissense predicts likely benign (score 0.1145) — an in-silico prediction, not a clinical call.

AOC1 p.Pro305Ser

c.913C>T · rs370642540 · VCV2388327

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1145 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1145	likely benign
REVEL	0.429	indeterminate
SaProt	LLR -7.50	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 1.9, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 4,735 bp · p 0.0054 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

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

Grpmax group 0.01% Admixed American · 6/59,906 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.000497% 8/1,609,780 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,984
Remaining individualsnot grpmax-eligible	0.00161%	62,288
European (non-Finnish)	8.49e-05%	1,178,212

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: AOC1
Protein: p.Pro305Ser
Coding: c.913C>T
MANE Select: NM_001091
dbSNP: rs370642540
Type: single nucleotide variant
Location: chr7:150857383 (GRCh38)
Gene constraint: LOEUF 1.253 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 5 PDB

Full AOC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AOC1 p.Asn659His Benign ★★ same type
AOC1 p.Ala347Val Uncertain significance ★ ⚠ same type
AOC1 p.Ala357Val Uncertain significance ★ ⚠ same type
AOC1 p.Ala487Thr Uncertain significance ★ ⚠ same type
AOC1 p.Ala565Val Uncertain significance ★ ⚠ same type
AOC1 p.Ala614Thr Uncertain significance ★ ⚠ same type
AOC1 p.Arg180Gly Uncertain significance ★ ⚠ same type
AOC1 p.Arg190Leu 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/aoc1-p-pro305ser (accessed [today's date]).

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