Is FIG4 p.Ile414= (c.1242T>C) pathogenic?

FIG4 p.Ile414= (c.1242T>C) is classified Benign/Likely benign in FIG4 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-01). Low-frequency (popmax 2.69%, afr); Associated with Inborn genetic diseases.

What condition is associated with FIG4 p.Ile414= (c.1242T>C)?

FIG4 p.Ile414= (c.1242T>C) is associated with Inborn genetic diseases, Yunis-Varon syndrome, Charcot-Marie-Tooth disease type 4J (ClinVar).

How common is FIG4 p.Ile414= (c.1242T>C) in the general population?

FIG4 p.Ile414= (c.1242T>C) is low-frequency (popmax 2.69%, afr) (gnomAD).

FIG4 p.Ile414=

c.1242T>C · rs61729087 · VCV355038

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.69%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -1.6, phastCons 0.001
Overall
CADD	7.114	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.69% African / African-American · 2,018/74,998 alleles

Filtering AF 2.59% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.55%

Overall 0.169% 2,724/1,613,216 alleles · low-frequency exomes 1,472/1,460,918 · genomes 1,252/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.69%	37
Admixed American	0.363%	275
Remaining individualsnot grpmax-eligible	0.306%	327
Middle Eastern	0.297%	337
European (non-Finnish)	0.0221%	4,518
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,920
South Asian	0.0121%	8,279
Finnishnot grpmax-eligible	0.00312%	32,014

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.Ile414=
Coding: c.1242T>C
MANE Select: NM_014845
dbSNP: rs61729087
Type: single nucleotide variant
Location: chr6:109760354 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB
Residue 414: the sac domain

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

Also linked: Yunis-Varon syndrome Charcot-Marie-Tooth disease type 4J amyotrophic lateral sclerosis type 11 bilateral parasagittal parieto-occipital polymicrogyria Charcot-Marie-Tooth disease Charcot-Marie-Tooth disease type 4

Similar variants

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.2376+2T>G 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-ile414 (accessed [today's date]).

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