What condition is associated with FGFR1 p.Val71Met (c.211G>A)?

FGFR1 p.Val71Met (c.211G>A) is associated with hypogonadotropic hypogonadism 2 with or without anosmia (ClinVar).

How common is FGFR1 p.Val71Met (c.211G>A) in the general population?

FGFR1 p.Val71Met (c.211G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FGFR1 p.Val71Met (c.211G>A)?

AlphaMissense predicts likely benign (score 0.0969) — an in-silico prediction, not a clinical call.

FGFR1 p.Val71Met

Q: Is FGFR1 p.Val71Met (c.211G>A) pathogenic?

FGFR1 p.Val71Met (c.211G>A) is classified Likely pathogenic in FGFR1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0969); Absent from gnomAD v4.1; Associated with hypogonadotropic hypogonadism 2 with or without anosmia.

c.211G>A · rs561300213 · VCV974817

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0969 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypogonadotropic hypogonadism 2 with or without anosmia

Computational evidence

Protein change
AlphaMissense	0.0969	likely benign ⚠ discordant with ClinVar
REVEL	0.098	moderately benign-leaning
SaProt	LLR -9.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 29 kb · p 0.67 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: FGFR1
Protein: p.Val71Met
Coding: c.211G>A
MANE Select: NM_023110
dbSNP: rs561300213
Type: single nucleotide variant
Location: chr8:38429829 (GRCh38)
Gene constraint: LOEUF 0.274 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 74.30 · 86 PDB
Residue 71: a β-strand; a disulfide bond; the ig-like c2-type 1 domain

Full FGFR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hypogonadotropic hypogonadism 2 with or without anosmia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FGFR1 p.Val71Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
FGFR1 p.Val71fs Pathogenic ★ same residue
FGFR1 p.Val71Ala Uncertain significance ★ ⚠ same residue
FGFR1 c.1977+1G>A Pathogenic/Likely pathogenic ★★ same condition
FGFR1 c.1977+1G>T Pathogenic/Likely pathogenic ★★ same condition
FGFR1 c.448+1G>A Likely pathogenic ★★ same condition
FGFR1 c.449-6G>A Likely pathogenic ★★ same condition
FGFR1 c.91+1G>A Pathogenic/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/fgfr1-p-val71met (accessed [today's date]).

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