Is GCNT2 p.Ser288Pro (c.862T>C) pathogenic?

GCNT2 p.Ser288Pro (c.862T>C) is classified Uncertain significance in GCNT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-14). AlphaMissense: ambiguous (0.3533); Ultra-rare (popmax 0.0195%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GCNT2 p.Ser288Pro (c.862T>C)?

GCNT2 p.Ser288Pro (c.862T>C) is associated with Inborn genetic diseases (ClinVar).

How common is GCNT2 p.Ser288Pro (c.862T>C) in the general population?

GCNT2 p.Ser288Pro (c.862T>C) is ultra-rare (popmax 0.0195%, nfe) (gnomAD).

What do computational predictors say about GCNT2 p.Ser288Pro (c.862T>C)?

AlphaMissense predicts ambiguous (score 0.3533) — an in-silico prediction, not a clinical call.

GCNT2 p.Ser288Pro

c.862T>C · rs771822241 · VCV2294675

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3533 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3533	ambiguous
REVEL	0.203	benign-leaning
SaProt	LLR -12.77	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.47	GERP -2.2
Regional constraint	o/e 1.19	unconstrained · MANE · 98 kb · p 1.9e-05 · regional, not allelic
Overall
CADD	23.3	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 0.0195% European (non-Finnish) · 230/1,179,996 alleles

Filtering AF 0.0174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.0148% 239/1,614,026 alleles · ultra-rare exomes 222/1,461,842 · genomes 17/152,184 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0195%	5,130
Remaining individualsnot grpmax-eligible	0.0096%	10,415
African / African-American	0.00267%	37,461
Finnishnot grpmax-eligible	0.00156%	64,038

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: GCNT2
Protein: p.Ser288Pro
Coding: c.862T>C
MANE Select: NM_145649
dbSNP: rs771822241
Type: single nucleotide variant
Location: chr6:10529773 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.66

Full GCNT2 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

GCNT2 p.Gly216Arg Uncertain significance ★★ same condition
GCNT2 p.Ala116Val Uncertain significance ★ same condition
GCNT2 p.Arg35Lys Uncertain significance ★ same condition
GCNT2 p.Asn189Lys Uncertain significance ★ ⚠ same condition
GCNT2 p.Asn214His Uncertain significance ★ ⚠ same condition
GCNT2 p.Gln142Leu Uncertain significance ★ ⚠ same condition
GCNT2 p.Gly352Arg Uncertain significance ★ same condition
GCNT2 p.His344Pro 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/gcnt2-p-ser288pro (accessed [today's date]).

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