Is FIG4 p.Pro851Ser (c.2551C>T) pathogenic?

FIG4 p.Pro851Ser (c.2551C>T) is classified Uncertain significance in FIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-30). AlphaMissense: likely benign (0.1077); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with FIG4 p.Pro851Ser (c.2551C>T)?

FIG4 p.Pro851Ser (c.2551C>T) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is FIG4 p.Pro851Ser (c.2551C>T) in the general population?

FIG4 p.Pro851Ser (c.2551C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FIG4 p.Pro851Ser (c.2551C>T)?

AlphaMissense predicts likely benign (score 0.1077) — an in-silico prediction, not a clinical call.

FIG4 p.Pro851Ser

c.2551C>T · rs773347231 · VCV1398148

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1077 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
AlphaMissense	0.1077	likely benign
REVEL	0.047	moderately benign-leaning
SaProt	LLR -6.47	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 3.9	GERP -0.044, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.33 · regional, not allelic
Overall
CADD	16.84	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

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: FIG4
Protein: p.Pro851Ser
Coding: c.2551C>T
MANE Select: NM_014845
dbSNP: rs773347231
Type: single nucleotide variant
Location: chr6:109825092 (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

Charcot-Marie-Tooth disease type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FIG4 p.Pro851Leu Uncertain significance ★★ ⚠ same residue
FIG4 p.Pro851Thr Uncertain significance ★ ⚠ same residue
FIG4 c.1040-1G>A Likely pathogenic ★★ same condition
FIG4 c.1584-1G>T Likely pathogenic ★★ same condition
FIG4 c.1948+1G>A Likely pathogenic ★★ same condition
FIG4 c.1949-10T>G Pathogenic/Likely pathogenic ★★ same condition
FIG4 c.2459+1G>A Pathogenic ★★ same condition
FIG4 c.877-2A>C Pathogenic/Likely pathogenic ★★ 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-pro851ser (accessed [today's date]).

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