Is FIG4 p.Pro797Leu (c.2390C>T) pathogenic?

FIG4 p.Pro797Leu (c.2390C>T) is classified Uncertain significance in FIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-26). AlphaMissense: likely benign (0.0994); Ultra-rare (popmax 0.0112%, eas); Associated with Inborn genetic diseases.

What condition is associated with FIG4 p.Pro797Leu (c.2390C>T)?

FIG4 p.Pro797Leu (c.2390C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FIG4 p.Pro797Leu (c.2390C>T) in the general population?

FIG4 p.Pro797Leu (c.2390C>T) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about FIG4 p.Pro797Leu (c.2390C>T)?

AlphaMissense predicts likely benign (score 0.0994) — an in-silico prediction, not a clinical call.

FIG4 p.Pro797Leu

c.2390C>T · VCV4025063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0994 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0994	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -6.37	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.33 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0112% East Asian · 5/44,758 alleles

Filtering AF 0.00436% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00277%

Overall 0.000375% 6/1,600,606 alleles · ultra-rare exomes 6/1,448,994 · genomes 0/151,612 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0112%	8,952
Remaining individualsnot grpmax-eligible	0.00161%	62,066

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: FIG4
Protein: p.Pro797Leu
Coding: c.2390C>T
MANE Select: NM_014845
Type: single nucleotide variant
Location: chr6:109792595 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB

Full FIG4 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

FIG4 c.2459+1G>A Pathogenic ★★ same condition
FIG4 p.Arg381Ter Pathogenic ★★ same condition
FIG4 p.Gln198Ter Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Leu643Ter Pathogenic ★★ same condition
FIG4 p.Trp246Ter Pathogenic ★★ same condition
FIG4 p.Tyr177Ter Pathogenic ★★ same condition
FIG4 c.2376+4C>T Uncertain significance ★★ same condition
FIG4 p.Ala308Val 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/fig4-p-pro797leu (accessed [today's date]).

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