Is AOC1 p.Phe439Ser (c.1316T>C) pathogenic?

AOC1 p.Phe439Ser (c.1316T>C) is classified Uncertain significance in AOC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: ambiguous (0.5592); Ultra-rare (popmax 0.0601%, afr).

How common is AOC1 p.Phe439Ser (c.1316T>C) in the general population?

AOC1 p.Phe439Ser (c.1316T>C) is ultra-rare (popmax 0.0601%, afr) (gnomAD).

What do computational predictors say about AOC1 p.Phe439Ser (c.1316T>C)?

AlphaMissense predicts ambiguous (score 0.5592) — an in-silico prediction, not a clinical call.

AOC1 p.Phe439Ser

c.1316T>C · VCV3876153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5592 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0601%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5592	ambiguous
REVEL	0.205	benign-leaning
SaProt	LLR -4.88	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 4,735 bp · p 0.0054 · regional, not allelic
Overall
CADD	23.9	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 0.0601% African / African-American · 45/74,932 alleles

Filtering AF 0.046% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0412%

Overall 0.00304% 49/1,614,078 alleles · ultra-rare exomes 23/1,461,864 · genomes 26/152,214 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0601%	1,665
Admixed American	0.00333%	30,001
Remaining individualsnot grpmax-eligible	0.0032%	31,245

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.Phe439Ser
Coding: c.1316T>C
MANE Select: NM_001091
Type: single nucleotide variant
Location: chr7:150857786 (GRCh38)
Gene constraint: LOEUF 1.253 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.43 · 5 PDB
Residue 439: a β-strand

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-phe439ser (accessed [today's date]).

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