Is ABCC10 p.Arg67Cys (c.199C>T) pathogenic?

ABCC10 p.Arg67Cys (c.199C>T) is classified Uncertain significance in ABCC10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-21). AlphaMissense: likely benign (0.1074); Ultra-rare (popmax 0.024%, afr).

How common is ABCC10 p.Arg67Cys (c.199C>T) in the general population?

ABCC10 p.Arg67Cys (c.199C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about ABCC10 p.Arg67Cys (c.199C>T)?

AlphaMissense predicts likely benign (score 0.1074) — an in-silico prediction, not a clinical call.

ABCC10 p.Arg67Cys

c.199C>T · rs375497152 · VCV2595383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1074	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -9.54	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 1.7	GERP 0.62, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 22 kb · p 4.2e-06 · regional, not allelic
Overall
CADD	23.2	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 0.024% African / African-American · 18/74,928 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00335% 54/1,614,098 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,163
South Asian	0.0198%	5,061
Middle Eastern	0.0164%	6,084
Admixed American	0.0117%	8,572
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,900
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000593%	168,577

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: ABCC10
Protein: p.Arg67Cys
Coding: c.199C>T
MANE Select: NM_001198934
dbSNP: rs375497152
Type: single nucleotide variant
Location: chr6:43432179 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32

Full ABCC10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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ABCC10 p.Ala1119Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1165Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1179Thr Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1324Pro Uncertain significance ★ ⚠ same type
ABCC10 p.Ala1324Ser Uncertain significance ★ ⚠ same type
ABCC10 p.Ala144Gly 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/abcc10-p-arg67cys (accessed [today's date]).

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