Is ABCC2 p.Tyr217Ser (c.650A>C) pathogenic?

ABCC2 p.Tyr217Ser (c.650A>C) is classified Uncertain significance in ABCC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-09-29). AlphaMissense: likely benign (0.3201); Ultra-rare (popmax 0.06%, amr); Associated with ABCC2-related disorder.

What condition is associated with ABCC2 p.Tyr217Ser (c.650A>C)?

ABCC2 p.Tyr217Ser (c.650A>C) is associated with ABCC2-related disorder (ClinVar).

How common is ABCC2 p.Tyr217Ser (c.650A>C) in the general population?

ABCC2 p.Tyr217Ser (c.650A>C) is ultra-rare (popmax 0.06%, amr) (gnomAD).

What do computational predictors say about ABCC2 p.Tyr217Ser (c.650A>C)?

AlphaMissense predicts likely benign (score 0.3201) — an in-silico prediction, not a clinical call.

ABCC2 p.Tyr217Ser

c.650A>C · rs202129492 · VCV291150

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3201 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.06%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCC2-related disorder

Computational evidence

Protein change
AlphaMissense	0.3201	likely benign
REVEL	0.713	pathogenic-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP 1.5, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 69 kb · p 0.48 · regional, not allelic
Overall
CADD	22.1	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 0.06% Admixed American · 36/60,022 alleles

Filtering AF 0.0444% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0392%

Overall 0.00223% 36/1,614,138 alleles · ultra-rare

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: ABCC2
Protein: p.Tyr217Ser
Coding: c.650A>C
MANE Select: NM_000392
dbSNP: rs202129492
Type: single nucleotide variant
Location: chr10:99797114 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40 · 16 PDB
Residue 217: an α-helix

Full ABCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ABCC2-related disorder

Similar variants

ABCC2 c.1967+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 c.3258+1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg1066Ter Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg1150His Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg393Trp Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Arg655Ter Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Gln1382Ter Pathogenic/Likely pathogenic ★★ same condition
ABCC2 p.Ser325Ter Pathogenic/Likely 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/abcc2-p-tyr217ser (accessed [today's date]).

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