Is FMN2 p.Ser610= (c.1830A>G) pathogenic?

FMN2 p.Ser610= (c.1830A>G) is classified Benign in FMN2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-26). Common (popmax 30.5%, sas) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, autosomal recessive 47.

What condition is associated with FMN2 p.Ser610= (c.1830A>G)?

FMN2 p.Ser610= (c.1830A>G) is associated with intellectual disability, autosomal recessive 47 (ClinVar).

FMN2 p.Ser610=

Q: How common is FMN2 p.Ser610= (c.1830A>G) in the general population?

FMN2 p.Ser610= (c.1830A>G) is common (popmax 30.5%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1830A>G · rs3765588 · VCV1285274

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 30.5%, sas) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, autosomal recessive 47

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -5.4	GERP -4.4
Overall
CADD	0.101	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 30.5% South Asian · 27,424/90,006 alleles

Filtering AF 30.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 30%

Overall 20.5% 329,542/1,609,032 alleles · common exomes 295,291/1,457,044 · genomes 34,251/151,988 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	30.5%	3
Middle Eastern	30.4%	3
African / African-American	29.1%	3
Ashkenazi Jewishnot grpmax-eligible	26.1%	4
Remaining individualsnot grpmax-eligible	21.8%	5
Finnishnot grpmax-eligible	20.3%	5
European (non-Finnish)	19.4%	5
East Asian	18.3%	5
Amishnot grpmax-eligible	14.7%	7
Admixed American	12.6%	8

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.Ser610=
Coding: c.1830A>G
MANE Select: NM_020066
dbSNP: rs3765588
Type: single nucleotide variant
Location: chr1:240177968 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB

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.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
FMN2 p.Ala1072= Benign ★★ 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-ser610 (accessed [today's date]).

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