Is FIBP p.Phe196Val (c.586T>G) pathogenic?

FIBP p.Phe196Val (c.586T>G) is classified Uncertain significance in FIBP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely pathogenic (0.7589); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FIBP p.Phe196Val (c.586T>G)?

FIBP p.Phe196Val (c.586T>G) is associated with Inborn genetic diseases (ClinVar).

How common is FIBP p.Phe196Val (c.586T>G) in the general population?

FIBP p.Phe196Val (c.586T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FIBP p.Phe196Val (c.586T>G)?

AlphaMissense predicts likely pathogenic (score 0.7589) — an in-silico prediction, not a clinical call.

FIBP p.Phe196Val

c.586T>G · rs2495607646 · VCV2252529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7589 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7589	likely pathogenic
REVEL	0.585	indeterminate
SaProt	LLR -10.43	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,441 bp · p 0.0063 · regional, not allelic
Overall
CADD	24.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: FIBP
Protein: p.Phe196Val
Coding: c.586T>G
MANE Select: NM_004214
dbSNP: rs2495607646
Type: single nucleotide variant
Location: chr11:65885590 (GRCh38)
Gene constraint: LOEUF 1.009 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.33

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FIBP p.Ala200Pro Uncertain significance ★ ⚠ same condition
FIBP p.Ala242Ser Uncertain significance ★ ⚠ same condition
FIBP p.Ala284Thr Uncertain significance ★ ⚠ same condition
FIBP p.Ala32Gly Uncertain significance ★ same condition
FIBP p.Ala72Ser Uncertain significance ★ ⚠ same condition
FIBP p.Ala72Thr Uncertain significance ★ ⚠ same condition
FIBP p.Arg143Trp Uncertain significance ★ ⚠ same condition
FIBP p.Arg152Gln Uncertain significance ★ ⚠ 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/fibp-p-phe196val (accessed [today's date]).

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