Is ABCC12 p.Tyr83Ser (c.248A>C) pathogenic?

ABCC12 p.Tyr83Ser (c.248A>C) is classified Uncertain significance in ABCC12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely benign (0.1785); Ultra-rare (popmax 0.0822%, mid).

How common is ABCC12 p.Tyr83Ser (c.248A>C) in the general population?

ABCC12 p.Tyr83Ser (c.248A>C) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

What do computational predictors say about ABCC12 p.Tyr83Ser (c.248A>C)?

AlphaMissense predicts likely benign (score 0.1785) — an in-silico prediction, not a clinical call.

ABCC12 p.Tyr83Ser

c.248A>C · rs200103308 · VCV2346034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1785 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1785	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -6.31	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 4.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 63 kb · p 0.2 · regional, not allelic
Overall
CADD	19.27	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 0.0822% Middle Eastern · 5/6,082 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00458% 74/1,614,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,216
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00667%	14,985
Admixed American	0.005%	20,001
European (non-Finnish)	0.00441%	22,693
South Asian	0.0011%	91,076

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: ABCC12
Protein: p.Tyr83Ser
Coding: c.248A>C
MANE Select: NM_001393797
dbSNP: rs200103308
Type: single nucleotide variant
Location: chr16:48143937 (GRCh38)
Gene constraint: LOEUF 1.022 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.09

Full ABCC12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC12 p.Thr1080Ala Uncertain significance ★★ ⚠ same type
ABCC12 p.Arg122= Likely benign ★★ same type
ABCC12 p.Gln831Ter Likely benign ★★ same type
ABCC12 p.Glu1191Ala Benign ★★ same type
ABCC12 p.Gly164Ter Benign/Likely benign ★★ same type
ABCC12 p.Lys1344= Benign ★★ same type
ABCC12 p.Lys894Met Benign ★★ same type
ABCC12 p.Phe54= Benign ★★ same type

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/abcc12-p-tyr83ser (accessed [today's date]).

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