Is FMN2 p.Ala471= (c.1413C>A) pathogenic?

FMN2 p.Ala471= (c.1413C>A) is classified Benign in FMN2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-26). Common (popmax 56.7%, mid) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, autosomal recessive 47.

What condition is associated with FMN2 p.Ala471= (c.1413C>A)?

FMN2 p.Ala471= (c.1413C>A) is associated with intellectual disability, autosomal recessive 47 (ClinVar).

FMN2 p.Ala471=

Q: How common is FMN2 p.Ala471= (c.1413C>A) in the general population?

FMN2 p.Ala471= (c.1413C>A) is common (popmax 56.7%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1413C>A · rs10926124 · VCV1285273

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 56.7%, mid) — 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.6	GERP -3.3
Overall
CADD	1.635	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 56.7% Middle Eastern · 3,320/5,852 alleles

Filtering AF 55.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 54.5%

Overall 48.1% 761,515/1,582,298 alleles · common exomes 701,847/1,430,172 · genomes 59,668/152,126 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	56.7%	2
Ashkenazi Jewishnot grpmax-eligible	55.6%	2
South Asian	51.2%	2
European (non-Finnish)	50.8%	2
Remaining individualsnot grpmax-eligible	48.1%	2
Amishnot grpmax-eligible	45.8%	2
Finnishnot grpmax-eligible	45.7%	2
Admixed American	39.6%	3
East Asian	34.7%	3
African / African-American	15.1%	7

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.Ala471=
Coding: c.1413C>A
MANE Select: NM_020066
dbSNP: rs10926124
Type: single nucleotide variant
Location: chr1:240093522 (GRCh38)
Gene constraint: LOEUF 0.51 · pLI 0.51 (gnomAD)
Structure: AlphaFold pLDDT 51.48 · 2 PDB
Residue 471: 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.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-ala471 (accessed [today's date]).

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