Is FIG4 p.Pro644= (c.1932A>G) pathogenic?

FIG4 p.Pro644= (c.1932A>G) is classified Likely benign in FIG4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-03). Very rare (popmax 0.00448%, eas); Associated with Charcot-Marie-Tooth disease type 4.

What condition is associated with FIG4 p.Pro644= (c.1932A>G)?

FIG4 p.Pro644= (c.1932A>G) is associated with Charcot-Marie-Tooth disease type 4 (ClinVar).

How common is FIG4 p.Pro644= (c.1932A>G) in the general population?

FIG4 p.Pro644= (c.1932A>G) is very rare (popmax 0.00448%, eas) (gnomAD).

FIG4 p.Pro644=

c.1932A>G · rs767919652 · VCV757839

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00448%, eas)

Conditions

Charcot-Marie-Tooth disease type 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.002	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -4.5
Overall
CADD	4.367	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00448% East Asian · 2/44,628 alleles

Filtering AF 0.000743% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000278%

Overall 0.000954% 15/1,572,844 alleles · very rare exomes 11/1,420,688 · genomes 4/152,156 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0172%	5,798
East Asiangrpmax	0.00448%	22,314
Remaining individualsnot grpmax-eligible	0.00163%	61,164
European (non-Finnish)	8.75e-05%	1,142,262

Finnish 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: FIG4
Protein: p.Pro644=
Coding: c.1932A>G
MANE Select: NM_014845
dbSNP: rs767919652
Type: single nucleotide variant
Location: chr6:109785012 (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.Pro644Gln 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
FIG4 p.Arg152Ter 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-pro644 (accessed [today's date]).

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