Is GNPTAB p.Ile826Val (c.2476A>G) pathogenic?

GNPTAB p.Ile826Val (c.2476A>G) is classified Likely benign in GNPTAB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-06). AlphaMissense: likely benign (0.0581); Very rare (popmax 0.0033%, sas); Associated with Inborn genetic diseases.

What condition is associated with GNPTAB p.Ile826Val (c.2476A>G)?

GNPTAB p.Ile826Val (c.2476A>G) is associated with Inborn genetic diseases (ClinVar).

How common is GNPTAB p.Ile826Val (c.2476A>G) in the general population?

GNPTAB p.Ile826Val (c.2476A>G) is very rare (popmax 0.0033%, sas) (gnomAD).

What do computational predictors say about GNPTAB p.Ile826Val (c.2476A>G)?

AlphaMissense predicts likely benign (score 0.0581) — an in-silico prediction, not a clinical call.

GNPTAB p.Ile826Val

c.2476A>G · rs553711125 · VCV2234845

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0581 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0581	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -3.1
Regional constraint	o/e 0.89	unconstrained · MANE · 84 kb · p 4.2e-05 · regional, not allelic
Overall
CADD	0.249	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

Grpmax group 0.0033% South Asian · 3/91,036 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00167% 27/1,613,632 alleles · very rare exomes 25/1,461,294 · genomes 2/152,338 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0033%	30,345
European (non-Finnish)	0.00186%	53,637
Admixed American	0.00167%	59,990
African / African-American	0.00133%	75,040

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: GNPTAB
Protein: p.Ile826Val
Coding: c.2476A>G
MANE Select: NM_024312
dbSNP: rs553711125
Type: single nucleotide variant
Location: chr12:101764441 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.15 · 5 PDB
Residue 826: a UniProt-annotated variant site (in mliiia)

Full GNPTAB 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

Similar variants

GNPTAB p.Gln205Ter Pathogenic/Likely pathogenic ★★ same condition
GNPTAB p.Ala1234Thr Uncertain significance ★★ ⚠ same condition
GNPTAB p.Asn524Asp Uncertain significance ★★ ⚠ same condition
GNPTAB p.Asp193Gly Uncertain significance ★★ ⚠ same condition
GNPTAB p.Asp407Asn Uncertain significance ★★ ⚠ same condition
GNPTAB p.Gln1006His Uncertain significance ★★ ⚠ same condition
GNPTAB p.Gln967Arg Uncertain significance ★★ ⚠ same condition
GNPTAB p.Glu1039Lys 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/gnptab-p-ile826val (accessed [today's date]).

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