Is GCSH p.Val82= (c.246T>A) pathogenic?

GCSH p.Val82= (c.246T>A) is classified Likely benign in GCSH (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). Very rare (popmax 0.00534%, afr); Associated with glycine encephalopathy.

What condition is associated with GCSH p.Val82= (c.246T>A)?

GCSH p.Val82= (c.246T>A) is associated with glycine encephalopathy (ClinVar).

How common is GCSH p.Val82= (c.246T>A) in the general population?

GCSH p.Val82= (c.246T>A) is very rare (popmax 0.00534%, afr) (gnomAD).

How is Glycine encephalopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

GCSH p.Val82=

c.246T>A · rs536733893 · VCV1140626

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00534%, afr)

Conditions

glycine encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -2.9, phastCons 1
Overall
CADD	6.316	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% African / African-American · 4/74,892 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000372% 6/1,611,734 alleles · very rare exomes 6/1,459,414 · genomes 0/152,320 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00534%	18,723
Remaining individualsnot grpmax-eligible	0.0032%	31,204

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: GCSH
Protein: p.Val82=
Coding: c.246T>A
MANE Select: NM_004483
dbSNP: rs536733893
Type: single nucleotide variant
Location: chr16:81087647 (GRCh38)
Gene constraint: LOEUF 1.537 · pLI 0.33 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.49 · 3 PDB
Residue 82: a β-strand; the lipoyl-binding domain; a UniProt-annotated variant site (in mmds7; likely pathogenic)

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

Disease context

glycine encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycine encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

GCSH p.Gln76Ter Pathogenic/Likely pathogenic ★★ same condition
GCSH p.Met1Val Pathogenic/Likely pathogenic ★★ same condition
GCSH p.Ala11Thr Uncertain significance ★★ ⚠ same condition
GCSH p.Ala2Pro Uncertain significance ★★ ⚠ same condition
GCSH p.Arg17Cys Uncertain significance ★★ ⚠ same condition
GCSH p.Arg7Trp Uncertain significance ★★ ⚠ same condition
GCSH p.Cys26Tyr Uncertain significance ★★ ⚠ same condition
GCSH p.Glu122Lys 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/gcsh-p-val82 (accessed [today's date]).

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