Is FH p.Ser334= (c.1002T>C) pathogenic?

FH p.Ser334= (c.1002T>C) is classified Benign/Likely benign in FH (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-21). Absent from gnomAD v4.1; Associated with hereditary leiomyomatosis and renal cell cancer.

How common is FH p.Ser334= (c.1002T>C) in the general population?

FH p.Ser334= (c.1002T>C) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary leiomyomatosis and renal cell cancer inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

FH p.Ser334=

Q: What condition is associated with FH p.Ser334= (c.1002T>C)?

FH p.Ser334= (c.1002T>C) is associated with hereditary leiomyomatosis and renal cell cancer, hereditary neoplastic syndrome (ClinVar).

c.1002T>C · rs2147916185 · VCV1082011

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary leiomyomatosis and renal cell cancer

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 1.1	GERP -1, phastCons 0.99
Overall
CADD	8.213	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FH
Protein: p.Ser334=
Coding: c.1002T>C
MANE Select: NM_000143
dbSNP: rs2147916185
Type: single nucleotide variant
Location: chr1:241504148 (GRCh38)
Gene constraint: LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.92 · 8 PDB
Residue 334: an α-helix

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

Disease context

hereditary leiomyomatosis and renal cell cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome

For Hereditary leiomyomatosis and renal cell cancer (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Elderly

Similar variants

FH p.Ser334Arg Likely pathogenic ★★ same residue
FH p.Ser334Gly Uncertain significance ★★ ⚠ same residue
FH p.Ser334fs Pathogenic ★★ same residue
FH c.1108+1G>A Pathogenic ★★ same condition
FH c.1108+1G>T Pathogenic/Likely pathogenic ★★ same condition
FH c.1236+1G>A Pathogenic/Likely pathogenic ★★ same condition
FH c.1236+1G>C Pathogenic ★★ same condition
FH c.1236+2T>G Pathogenic ★★ 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/fh-p-ser334 (accessed [today's date]).

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