Is FMO4 p.Ser534Pro (c.1600T>C) pathogenic?

FMO4 p.Ser534Pro (c.1600T>C) is classified Benign in FMO4 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-12-28). AlphaMissense: likely benign (0.0811); Low-frequency (popmax 2.81%, afr).

How common is FMO4 p.Ser534Pro (c.1600T>C) in the general population?

FMO4 p.Ser534Pro (c.1600T>C) is low-frequency (popmax 2.81%, afr) (gnomAD).

What do computational predictors say about FMO4 p.Ser534Pro (c.1600T>C)?

AlphaMissense predicts likely benign (score 0.0811) — an in-silico prediction, not a clinical call.

FMO4 p.Ser534Pro

c.1600T>C · rs75661671 · VCV780279

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0811 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.81%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0811	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -6.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -0.72, phastCons 0.77
Regional constraint	o/e 0.95	unconstrained · MANE · 22 kb · p 0.21 · regional, not allelic
Overall
CADD	16.31	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 2.81% African / African-American · 2,107/75,030 alleles

Filtering AF 2.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.67%

Overall 0.147% 2,367/1,613,884 alleles · low-frequency exomes 1,150/1,461,560 · genomes 1,217/152,324 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.81%	36
Remaining individualsnot grpmax-eligible	0.211%	473
Admixed American	0.169%	593
Middle Eastern	0.116%	865
South Asian	0.00439%	22,767
European (non-Finnish)	0.00136%	73,745

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: FMO4
Protein: p.Ser534Pro
Coding: c.1600T>C
MANE Select: NM_002022
dbSNP: rs75661671
Type: single nucleotide variant
Location: chr1:171341762 (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.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
FMO4 p.Arg237Thr 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-ser534pro (accessed [today's date]).

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