Is FIBP p.Phe178Val (c.532T>G) pathogenic?

FIBP p.Phe178Val (c.532T>G) is classified Uncertain significance in FIBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: likely pathogenic (0.9484); Very rare (popmax 0.00878%, sas).

How common is FIBP p.Phe178Val (c.532T>G) in the general population?

FIBP p.Phe178Val (c.532T>G) is very rare (popmax 0.00878%, sas) (gnomAD).

What do computational predictors say about FIBP p.Phe178Val (c.532T>G)?

AlphaMissense predicts likely pathogenic (score 0.9484) — an in-silico prediction, not a clinical call.

FIBP p.Phe178Val

c.532T>G · VCV4282398

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00878%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9484	likely pathogenic
REVEL	0.73	pathogenic-leaning
SaProt	LLR -13.53	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 1.6, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 4,441 bp · p 0.0063 · regional, not allelic
Overall
CADD	27.9	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 0.00878% South Asian · 8/91,076 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.00242% 39/1,613,952 alleles · very rare exomes 37/1,461,738 · genomes 2/152,214 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00878%	11,385
Admixed American	0.00667%	15,000
European (non-Finnish)	0.00229%	43,702

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: FIBP
Protein: p.Phe178Val
Coding: c.532T>G
MANE Select: NM_004214
Type: single nucleotide variant
Location: chr11:65885644 (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

Similar variants

FIBP p.Asp223Gly Uncertain significance ★★ same type
FIBP p.Leu352Arg Uncertain significance ★★ ⚠ same type
FIBP c.1004+33T>C Benign ★★ same type
FIBP p.Ala50= Benign ★★ same type
FIBP p.Gly187= Likely benign ★★ same type
FIBP p.Gly263= Likely benign ★★ same type
FIBP p.Leu240= Benign/Likely benign ★★ same type
FIBP p.Leu299= Benign/Likely benign ★★ 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/fibp-p-phe178val (accessed [today's date]).

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