Is PGAP1 p.Tyr626Cys (c.1877A>G) pathogenic?

PGAP1 p.Tyr626Cys (c.1877A>G) is classified Uncertain significance in PGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-26). AlphaMissense: likely benign (0.2531); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PGAP1 p.Tyr626Cys (c.1877A>G)?

PGAP1 p.Tyr626Cys (c.1877A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PGAP1 p.Tyr626Cys (c.1877A>G) in the general population?

PGAP1 p.Tyr626Cys (c.1877A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PGAP1 p.Tyr626Cys (c.1877A>G)?

AlphaMissense predicts likely benign (score 0.2531) — an in-silico prediction, not a clinical call.

PGAP1 p.Tyr626Cys

c.1877A>G · rs2469098372 · VCV2313334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2531 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2531	likely benign
REVEL	0.171	moderately benign-leaning
SaProt	LLR -10.95	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.067, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 85 kb · p 0.0064 · regional, not allelic
Overall
CADD	24.5	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

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: PGAP1
Protein: p.Tyr626Cys
Coding: c.1877A>G
MANE Select: NM_024989
dbSNP: rs2469098372
Type: single nucleotide variant
Location: chr2:196848022 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 89.15

Full PGAP1 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

PGAP1 p.Tyr626His Conflicting classifications of pathogenicity ★ ⚠ same residue
PGAP1 p.Ala298Thr Uncertain significance ★★ ⚠ same condition
PGAP1 p.Ala714Val Uncertain significance ★★ ⚠ same condition
PGAP1 p.Ala864Val Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg803His Uncertain significance ★★ ⚠ same condition
PGAP1 p.Arg814Cys Uncertain significance ★★ ⚠ same condition
PGAP1 p.Asn129Ser Uncertain significance ★★ ⚠ same condition
PGAP1 p.Asn363Asp 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/pgap1-p-tyr626cys (accessed [today's date]).

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