Is FBP2 p.Val86Ala (c.257T>C) pathogenic?

FBP2 p.Val86Ala (c.257T>C) is classified Benign in FBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-01). AlphaMissense: likely pathogenic (0.5862); Rare (popmax 0.154%, sas).

How common is FBP2 p.Val86Ala (c.257T>C) in the general population?

FBP2 p.Val86Ala (c.257T>C) is rare (popmax 0.154%, sas) (gnomAD).

What do computational predictors say about FBP2 p.Val86Ala (c.257T>C)?

AlphaMissense predicts likely pathogenic (score 0.5862) — an in-silico prediction, not a clinical call.

FBP2 p.Val86Ala

c.257T>C · rs201607341 · VCV2673178

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5862 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.154%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5862	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -8.98	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 35 kb · p 0.47 · regional, not allelic
Overall
CADD	24.3	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

Grpmax group 0.154% South Asian · 140/91,076 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.125%

Overall 0.026% 419/1,614,016 alleles · rare exomes 397/1,461,792 · genomes 22/152,224 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.466%	215
South Asiangrpmax	0.154%	651
Middle Eastern	0.099%	1,010
Remaining individualsnot grpmax-eligible	0.0464%	2,155
European (non-Finnish)	0.00898%	11,131

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: FBP2
Protein: p.Val86Ala
Coding: c.257T>C
MANE Select: NM_003837
dbSNP: rs201607341
Type: single nucleotide variant
Location: chr9:94587383 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 14 PDB
Residue 86: a UniProt-annotated variant site (in); an α-helix

Full FBP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FBP2 p.Ile133Val Uncertain significance ★★ ⚠ same type
FBP2 p.Ser211Asn Benign ★★ same type
FBP2 p.Ter340Trp Benign ★★ same type
FBP2 p.Thr225= Benign ★★ same type
FBP2 p.Ala131Asp Uncertain significance ★ ⚠ same type
FBP2 p.Ala166Thr Uncertain significance ★ same type
FBP2 p.Ala25Ser Uncertain significance ★ ⚠ same type
FBP2 p.Arg141Lys Uncertain significance ★ ⚠ same type

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/fbp2-p-val86ala (accessed [today's date]).

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