Is FH p.Val396Ala (c.1187_1188delinsCT) pathogenic?

FH p.Val396Ala (c.11871188delinsCT) is classified Uncertain significance in FH (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-24). No gnomAD frequency available for this variant; Associated with hereditary neoplastic syndrome.

What condition is associated with FH p.Val396Ala (c.1187_1188delinsCT)?

FH p.Val396Ala (c.1187_1188delinsCT) is associated with hereditary neoplastic syndrome (ClinVar).

How common is FH p.Val396Ala (c.1187_1188delinsCT) in the general population?

FH p.Val396Ala (c.1187_1188delinsCT) is no gnomAD frequency available for this variant (gnomAD).

FH p.Val396Ala

c.1187_1188delinsCT · rs2527316596 · VCV1743640

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.6	GERP -5.4
Regional constraint	o/e 0.75	unconstrained · MANE · 16 kb · p 7.5e-09 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Val396Ala
Coding: c.1187_1188delinsCT
MANE Select: NM_000143
dbSNP: rs2527316596
Type: Indel
Location: chr1:241502491 (GRCh38)
Gene constraint: LOEUF 0.599 · pLI 0.27 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.92 · 8 PDB
Residue 396: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FH p.Val396Leu Uncertain significance ★★ same residue
FH p.Val396= Benign/Likely benign ★★ same residue
FH p.Val396Ile Uncertain significance ★ ⚠ same residue
FH c.1391-1_1391delinsTT Pathogenic/Likely pathogenic ★★ same condition
FH p.Ala220Leu Uncertain significance ★★ same condition
FH c.129_132+5delinsGAGC Pathogenic ★ same condition
FH c.731_738+3delinsAAAT Pathogenic ★ same condition
FH c.739-17_754delinsGAATTGCATAT Likely 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-val396ala (accessed [today's date]).

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