Is ABCC5 p.Cys594= (c.1782T>C) pathogenic?

ABCC5 p.Cys594= (c.1782T>C) is classified Benign in ABCC5 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-27). Common (popmax 86.4%, eas) — too common for a highly-penetrant pathogenic allele.

ABCC5 p.Cys594=

Q: How common is ABCC5 p.Cys594= (c.1782T>C) in the general population?

ABCC5 p.Cys594= (c.1782T>C) is common (popmax 86.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1782T>C · rs939336 · VCV1252281

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 86.4%, eas) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.003	GERP -5.5, phastCons 0.022
Overall
CADD	3.215	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 86.4% East Asian · 38,753/44,850 alleles

Filtering AF 85.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 85.4%

Overall 57.1% 920,588/1,611,950 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	86.4%	1
African / African-American	77%	1
Middle Eastern	58.7%	2
Remaining individualsnot grpmax-eligible	57.9%	2
European (non-Finnish)	55.4%	2
Ashkenazi Jewishnot grpmax-eligible	55.2%	2
South Asian	54.7%	2
Admixed American	54.4%	2
Finnishnot grpmax-eligible	50.8%	2
Amishnot grpmax-eligible	45.7%	2

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: ABCC5
Protein: p.Cys594=
Coding: c.1782T>C
MANE Select: NM_005688
dbSNP: rs939336
Type: single nucleotide variant
Location: chr3:183967746 (GRCh38)
Gene constraint: LOEUF 0.455 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 78.13 · 6 PDB
Residue 594: the abc transporter 1 domain; a β-strand

Full ABCC5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCC5 c.825+10G>A Benign ★★ same type
ABCC5 p.Ala1008Ser Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1150Thr Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1182Val Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1302Gly Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1343Thr Uncertain significance ★ ⚠ same type
ABCC5 p.Ala1434Thr Uncertain significance ★ ⚠ same type
ABCC5 p.Ala164Thr Uncertain significance ★ ⚠ 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/abcc5-p-cys594 (accessed [today's date]).

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