Is FIG4 p.Asp783Val (c.2348A>T) pathogenic?

FIG4 p.Asp783Val (c.2348A>T) is classified Conflicting classifications of pathogenicity in FIG4 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2016-01-06). AlphaMissense: likely benign (0.1574); Absent from gnomAD v4.1; Associated with bilateral parasagittal parieto-occipital polymicrogyria.

What condition is associated with FIG4 p.Asp783Val (c.2348A>T)?

FIG4 p.Asp783Val (c.2348A>T) is associated with bilateral parasagittal parieto-occipital polymicrogyria, Yunis-Varon syndrome (ClinVar).

How common is FIG4 p.Asp783Val (c.2348A>T) in the general population?

FIG4 p.Asp783Val (c.2348A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FIG4 p.Asp783Val (c.2348A>T)?

AlphaMissense predicts likely benign (score 0.1574) — an in-silico prediction, not a clinical call.

FIG4 p.Asp783Val

c.2348A>T · rs587777716 · VCV156017

Conflicting classifications of pathogenicity No assertion criteria

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1574 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

bilateral parasagittal parieto-occipital polymicrogyria

Computational evidence

Protein change
AlphaMissense	0.1574	likely benign
REVEL	0.749	pathogenic-leaning
SaProt	LLR -5.53	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.4	GERP 2.3, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 48 kb · p 0.33 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

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.Asp783Val
Coding: c.2348A>T
MANE Select: NM_014845
dbSNP: rs587777716
Type: single nucleotide variant
Location: chr6:109791543 (GRCh38)
Gene constraint: LOEUF 0.966 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.65 · 1 PDB
Residue 783: a UniProt-annotated variant site (in btop; partial loss of function); the 'disordered' region

Full FIG4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

bilateral parasagittal parieto-occipital polymicrogyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Yunis-Varon syndrome

Similar variants

FIG4 c.1040-1G>A Likely pathogenic ★★ same condition
FIG4 c.2376+2T>G Likely pathogenic ★★ same condition
FIG4 p.Arg381Ter Pathogenic ★★ same condition
FIG4 p.Gln823Ter Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Ile41Thr Pathogenic/Likely pathogenic ★★ same condition
FIG4 p.Trp246Ter Pathogenic ★★ same condition
FIG4 p.Arg699Cys Uncertain significance ★★ same condition
FIG4 p.Arg699His 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-asp783val (accessed [today's date]).

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