Is ADGRG1 p.Ser642Phe (c.1925C>T) pathogenic?

ADGRG1 p.Ser642Phe (c.1925C>T) is classified Likely pathogenic in ADGRG1 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9498); Absent from gnomAD v4.1; Associated with bilateral frontoparietal polymicrogyria.

What condition is associated with ADGRG1 p.Ser642Phe (c.1925C>T)?

ADGRG1 p.Ser642Phe (c.1925C>T) is associated with bilateral frontoparietal polymicrogyria (ClinVar).

How common is ADGRG1 p.Ser642Phe (c.1925C>T) in the general population?

ADGRG1 p.Ser642Phe (c.1925C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ADGRG1 p.Ser642Phe (c.1925C>T)?

AlphaMissense predicts likely pathogenic (score 0.9498) — an in-silico prediction, not a clinical call.

ADGRG1 p.Ser642Phe

c.1925C>T · rs2148610313 · VCV977829

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9498 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

bilateral frontoparietal polymicrogyria

Computational evidence

Protein change
AlphaMissense	0.9498	likely pathogenic ✓ concordant with ClinVar · top 4% in ADGRG1
REVEL	0.46	indeterminate
SaProt	LLR -13.86	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 13 kb · p 0.0093 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S648F vs ClinVar S642F) — verify the residue.

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: ADGRG1
Protein: p.Ser642Phe
Coding: c.1925C>T
MANE Select: NM_201525
dbSNP: rs2148610313
Type: single nucleotide variant
Location: chr16:57661957 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.29 · 2 PDB
Residue 642: a UniProt-annotated variant site (in cdcbm14a); a UniProt-annotated variant site (in cdcbm14a; uncertain significance); an α-helix

Full ADGRG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

bilateral frontoparietal polymicrogyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADGRG1 c.1933+1G>T Pathogenic/Likely pathogenic ★★ same condition
ADGRG1 c.488-2A>G Likely pathogenic ★★ same condition
ADGRG1 c.620+1G>A Pathogenic/Likely pathogenic ★★ same condition
ADGRG1 p.Arg271Ter Pathogenic ★★ same condition
ADGRG1 p.Arg38Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
ADGRG1 p.Arg470Ter Pathogenic ★★ same condition
ADGRG1 p.Arg496Ter Pathogenic ★★ same condition
ADGRG1 p.Arg559Trp 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/adgrg1-p-ser642phe (accessed [today's date]).

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