Is FMO4 p.Lys115Thr (c.344A>C) pathogenic?

FMO4 p.Lys115Thr (c.344A>C) is classified Uncertain significance in FMO4 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-27). AlphaMissense: likely benign (0.3197); Very rare (popmax 0.000933%, nfe).

How common is FMO4 p.Lys115Thr (c.344A>C) in the general population?

FMO4 p.Lys115Thr (c.344A>C) is very rare (popmax 0.000933%, nfe) (gnomAD).

What do computational predictors say about FMO4 p.Lys115Thr (c.344A>C)?

AlphaMissense predicts likely benign (score 0.3197) — an in-silico prediction, not a clinical call.

FMO4 p.Lys115Thr

c.344A>C · VCV4828190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3197 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000933%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3197	likely benign
REVEL	0.308	indeterminate
SaProt	LLR -11.41	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.9	GERP 0.54, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 22 kb · p 0.21 · regional, not allelic
Overall
CADD	20.9	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 0.000933% European (non-Finnish) · 11/1,179,296 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,612,166 alleles · very rare exomes 5/1,459,958 · genomes 6/152,208 · joint denominator

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.Lys115Thr
Coding: c.344A>C
MANE Select: NM_002022
Type: single nucleotide variant
Location: chr1:171324160 (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-lys115thr (accessed [today's date]).

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