Is FMN2 p.Ser295Phe (c.884C>T) pathogenic?

FMN2 p.Ser295Phe (c.884C>T) is classified Uncertain significance in FMN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-20). AlphaMissense: likely benign (0.1402); Very rare (popmax 0.00948%, sas); Associated with intellectual disability, autosomal recessive 47.

What condition is associated with FMN2 p.Ser295Phe (c.884C>T)?

FMN2 p.Ser295Phe (c.884C>T) is associated with intellectual disability, autosomal recessive 47 (ClinVar).

How common is FMN2 p.Ser295Phe (c.884C>T) in the general population?

FMN2 p.Ser295Phe (c.884C>T) is very rare (popmax 0.00948%, sas) (gnomAD).

What do computational predictors say about FMN2 p.Ser295Phe (c.884C>T)?

AlphaMissense predicts likely benign (score 0.1402) — an in-silico prediction, not a clinical call.

FMN2 p.Ser295Phe

c.884C>T · rs779845544 · VCV2441895

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1402 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00948%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability, autosomal recessive 47

Computational evidence

Protein change
AlphaMissense	0.1402	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -8.82	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 2.2	GERP 1.5, phastCons 0.011
Regional constraint	o/e 0.95	unconstrained · MANE · 31 kb · p 0.15 · regional, not allelic
Overall
CADD	18.41	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00948% South Asian · 6/63,312 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00273%

Overall 0.000785% 11/1,401,374 alleles · very rare exomes 11/1,249,108 · genomes 0/152,266 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00948%	10,552
Remaining individualsnot grpmax-eligible	0.00186%	53,908
European (non-Finnish)	0.000368%	271,753

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: FMN2
Protein: p.Ser295Phe
Coding: c.884C>T
MANE Select: NM_020066
dbSNP: rs779845544
Type: single nucleotide variant
Location: chr1:240092993 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 295: the 'disordered' region

Full FMN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal recessive 47 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FMN2 p.Ser295Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
FMN2 p.Ile183Phe Likely pathogenic ★★ ⚠ same condition
FMN2 p.Asp352Tyr Uncertain significance ★★ ⚠ same condition
FMN2 p.Gln192Leu Uncertain significance ★★ ⚠ same condition
FMN2 p.Gln210Arg Uncertain significance ★★ ⚠ same condition
FMN2 p.Pro1044Leu Uncertain significance ★★ ⚠ same condition
FMN2 p.Pro1187Leu Uncertain significance ★★ ⚠ same condition
FMN2 p.Thr415Ile Uncertain significance ★★ ⚠ same condition

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/fmn2-p-ser295phe (accessed [today's date]).

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