Is FGF8 p.Val65= (c.195G>C) pathogenic?

FGF8 p.Val65= (c.195G>C) is classified Uncertain significance in FGF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). Absent from gnomAD v4.1; Associated with hypogonadotropic hypogonadism 6 with or without anosmia.

What condition is associated with FGF8 p.Val65= (c.195G>C)?

FGF8 p.Val65= (c.195G>C) is associated with hypogonadotropic hypogonadism 6 with or without anosmia (ClinVar).

How common is FGF8 p.Val65= (c.195G>C) in the general population?

FGF8 p.Val65= (c.195G>C) is absent from gnomAD v4.1 (gnomAD).

FGF8 p.Val65=

c.195G>C · rs2539367130 · VCV3238944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hypogonadotropic hypogonadism 6 with or without anosmia

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 7.6	GERP 2.3, phastCons 1
Overall
CADD	15.12	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: FGF8
Protein: p.Val65=
Coding: c.195G>C
MANE Select: NM_033163
dbSNP: rs2539367130
Type: single nucleotide variant
Location: chr10:101774874 (GRCh38)
Gene constraint: LOEUF 0.765 · pLI 0.06 (gnomAD)
Structure: AlphaFold pLDDT 81.34 · 1 PDB
Residue 65: a β-strand

Full FGF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypogonadotropic hypogonadism 6 with or without anosmia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGF8 p.Arg129Ter Pathogenic/Likely pathogenic ★★ same condition
FGF8 p.Thr119Met Likely pathogenic ★★ same condition
FGF8 p.Ala147Thr Uncertain significance ★★ ⚠ same condition
FGF8 p.Gln47His Uncertain significance ★★ ⚠ same condition
FGF8 p.Gly151Ser Uncertain significance ★★ ⚠ same condition
FGF8 c.444+19G>A Benign/Likely benign ★★ same condition
FGF8 c.445-62G>A Benign ★★ same condition
FGF8 p.Arg127Ter 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/fgf8-p-val65 (accessed [today's date]).

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