Is GLDC p.Ala7Val (c.20C>T) pathogenic?

GLDC p.Ala7Val (c.20C>T) is classified Uncertain significance in GLDC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-04-13). AlphaMissense: likely benign (0.1185); Very rare (popmax 0.00542%, sas); Associated with Inborn genetic diseases.

What condition is associated with GLDC p.Ala7Val (c.20C>T)?

GLDC p.Ala7Val (c.20C>T) is associated with Inborn genetic diseases, glycine encephalopathy (ClinVar).

How common is GLDC p.Ala7Val (c.20C>T) in the general population?

GLDC p.Ala7Val (c.20C>T) is very rare (popmax 0.00542%, sas) (gnomAD).

What do computational predictors say about GLDC p.Ala7Val (c.20C>T)?

AlphaMissense predicts likely benign (score 0.1185) — an in-silico prediction, not a clinical call.

GLDC p.Ala7Val

c.20C>T · rs1420734296 · VCV846074

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1185 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00542%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1185	likely benign
REVEL	0.372	indeterminate
SaProt	LLR -6.51	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP -1.5, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 112 kb · p 0.00071 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00542% South Asian · 2/36,874 alleles

Filtering AF 0.000899% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000336%

Overall 0.000158% 2/1,269,178 alleles · very rare exomes 1/1,118,084 · genomes 1/151,094 · joint denominator

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: GLDC
Protein: p.Ala7Val
Coding: c.20C>T
MANE Select: NM_000170
dbSNP: rs1420734296
Type: single nucleotide variant
Location: chr9:6645480 (GRCh38)
Gene constraint: LOEUF 1.09 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.50 · 3 PDB

Full GLDC 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: glycine encephalopathy

Similar variants

GLDC c.1401+1G>A Pathogenic/Likely pathogenic ★★ same condition
GLDC c.1580+2T>G Pathogenic ★★ same condition
GLDC c.1851-1G>A Pathogenic ★★ same condition
GLDC c.2053-2A>G Likely pathogenic ★★ same condition
GLDC c.2203-2A>G Pathogenic/Likely pathogenic ★★ same condition
GLDC c.2315+2T>A Pathogenic/Likely pathogenic ★★ same condition
GLDC c.2315+2T>G Pathogenic/Likely pathogenic ★★ same condition
GLDC c.2316-1G>A 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/gldc-p-ala7val (accessed [today's date]).

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