Is FBP2 p.Phe118Ser (c.353T>C) pathogenic?

FBP2 p.Phe118Ser (c.353T>C) is classified Uncertain significance in FBP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-12). AlphaMissense: likely pathogenic (0.97); Ultra-rare (popmax 0.0329%, mid).

How common is FBP2 p.Phe118Ser (c.353T>C) in the general population?

FBP2 p.Phe118Ser (c.353T>C) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about FBP2 p.Phe118Ser (c.353T>C)?

AlphaMissense predicts likely pathogenic (score 0.97) — an in-silico prediction, not a clinical call.

FBP2 p.Phe118Ser

c.353T>C · VCV3513709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.97 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.97	likely pathogenic
REVEL	0.927	moderately pathogenic-leaning
SaProt	LLR -14.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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	29.1	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

Grpmax group 0.0329% Middle Eastern · 2/6,078 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.00279% 45/1,612,652 alleles · ultra-rare exomes 38/1,460,444 · genomes 7/152,208 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
European (non-Finnish)	0.00339%	29,469
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,444
African / African-American	0.00134%	74,886

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.Phe118Ser
Coding: c.353T>C
MANE Select: NM_003837
Type: single nucleotide variant
Location: chr9:94584650 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 14 PDB
Residue 118: a β-strand

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-phe118ser (accessed [today's date]).

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