Is FH p.Ile487= (c.1461C>A) pathogenic?

FH p.Ile487= (c.1461C>A) is classified Likely benign in FH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-07). No allele count reported in gnomAD v4.1 (AN 1,613,596).

How common is FH p.Ile487= (c.1461C>A) in the general population?

FH p.Ile487= (c.1461C>A) is no allele count reported in gnomAD v4.1 (AN 1,613,596) (gnomAD).

FH p.Ile487=

c.1461C>A · rs377091029 · VCV1554310

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,596)

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 0.096	GERP -5.6, phastCons 0.099
Overall
CADD	1.546	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,596). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: FH
Protein: p.Ile487=
Coding: c.1461C>A
MANE Select: NM_000143
dbSNP: rs377091029
Type: single nucleotide variant
Location: chr1:241497900 (GRCh38)
Gene constraint: LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.92 · 8 PDB
Residue 487: an α-helix

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

Similar variants

FH p.Ile487Phe Uncertain significance ★★ same residue
FH p.Ile487Val Uncertain significance ★★ ⚠ same residue
FH p.Ile487Asn Uncertain significance ★ ⚠ same residue
FH p.Ile487Met Uncertain significance ★ ⚠ same residue
FH p.Ile487Ser Uncertain significance ★ ⚠ same residue
FH p.Ile487Thr Uncertain significance ★ ⚠ same residue
FH c.1108+1G>A Pathogenic ★★ same type
FH c.1108+1G>T Pathogenic/Likely pathogenic ★★ 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/fh-p-ile487 (accessed [today's date]).

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