Is FMO4 p.Ser34Ile (c.101G>T) pathogenic?

FMO4 p.Ser34Ile (c.101G>T) is classified Uncertain significance in FMO4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: ambiguous (0.4086); Absent from gnomAD v4.1.

How common is FMO4 p.Ser34Ile (c.101G>T) in the general population?

FMO4 p.Ser34Ile (c.101G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FMO4 p.Ser34Ile (c.101G>T)?

AlphaMissense predicts ambiguous (score 0.4086) — an in-silico prediction, not a clinical call.

FMO4 p.Ser34Ile

c.101G>T · VCV3850970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4086 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4086	ambiguous
REVEL	0.293	indeterminate
SaProt	LLR -11.39	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.51	GERP 1.9, phastCons 0.044
Regional constraint	o/e 0.95	unconstrained · MANE · 22 kb · p 0.21 · regional, not allelic
Overall
CADD	23.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FMO4
Protein: p.Ser34Ile
Coding: c.101G>T
MANE Select: NM_002022
Type: single nucleotide variant
Location: chr1:171319926 (GRCh38)
Gene constraint: LOEUF 1.329 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.52

Full FMO4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FMO4 c.1180+3A>G Uncertain significance ★★ same type
FMO4 p.Gly372Ser Likely benign ★★ same type
FMO4 p.Leu221His Likely benign ★★ same type
FMO4 p.Ser534Pro Benign ★★ same type
FMO4 p.Ala159Asp Uncertain significance ★ ⚠ same type
FMO4 p.Arg116Ser Uncertain significance ★ ⚠ same type
FMO4 p.Arg186Cys Uncertain significance ★ ⚠ same type
FMO4 p.Arg205Gln 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/fmo4-p-ser34ile (accessed [today's date]).

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