Is PPOX p.Ser385Phe (c.1154C>T) pathogenic?

PPOX p.Ser385Phe (c.1154C>T) is classified Uncertain significance in PPOX (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-22). AlphaMissense: ambiguous (0.387); Very rare (popmax 0.0011%, sas).

How common is PPOX p.Ser385Phe (c.1154C>T) in the general population?

PPOX p.Ser385Phe (c.1154C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PPOX p.Ser385Phe (c.1154C>T)?

AlphaMissense predicts ambiguous (score 0.387) — an in-silico prediction, not a clinical call.

PPOX p.Ser385Phe

c.1154C>T · rs1484062472 · VCV2102031

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.387 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
AlphaMissense	0.387	ambiguous
REVEL	0.538	indeterminate
SaProt	LLR -14.90	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.62	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 0.92
Overall
CADD	34.0	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 0.0011% South Asian · 1/91,086 alleles

Overall 0.000124% 2/1,614,148 alleles · very rare exomes 2/1,461,890 · genomes 0/152,258 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,086
European (non-Finnish)	8.47e-05%	1,180,045

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: PPOX
Protein: p.Ser385Phe
Coding: c.1154C>T
MANE Select: NM_001122764
dbSNP: rs1484062472
Type: single nucleotide variant
Location: chr1:161170675 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 95.39 · 3 PDB

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

Similar variants

PPOX c.-9G>A Likely pathogenic ★★ same type
PPOX p.Arg168His Pathogenic/Likely pathogenic ★★ ⚠ same type
PPOX p.Arg59Trp Pathogenic ★★ same type
PPOX p.Gln189Ter Pathogenic ★★ same type
PPOX p.Gln435Ter Pathogenic/Likely pathogenic ★★ same type
PPOX p.Glu133Ter Pathogenic ★★ same type
PPOX p.Glu191Ter Pathogenic/Likely pathogenic ★★ same type
PPOX c.471+3G>A 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/ppox-p-ser385phe (accessed [today's date]).

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