Is ABCA9 p.Arg67Cys (c.199C>T) pathogenic?

ABCA9 p.Arg67Cys (c.199C>T) is classified Uncertain significance in ABCA9 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: likely benign (0.1896); Ultra-rare (popmax 0.0329%, mid).

How common is ABCA9 p.Arg67Cys (c.199C>T) in the general population?

ABCA9 p.Arg67Cys (c.199C>T) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about ABCA9 p.Arg67Cys (c.199C>T)?

AlphaMissense predicts likely benign (score 0.1896) — an in-silico prediction, not a clinical call.

ABCA9 p.Arg67Cys

c.199C>T · VCV3968967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1896 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1896	likely benign
REVEL	0.388	indeterminate
SaProt	LLR -11.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP -0.82
Regional constraint	o/e 0.94	unconstrained · MANE · 75 kb · p 0.014 · regional, not allelic
Overall
CADD	21.7	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 0.0329% Middle Eastern · 2/6,072 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00309%

Overall 0.0026% 42/1,612,520 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,036
African / African-American	0.00936%	10,688
East Asian	0.00893%	11,198
Remaining individualsnot grpmax-eligible	0.00641%	15,604
European (non-Finnish)	0.00204%	49,127
South Asian	0.0011%	91,034

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: ABCA9
Protein: p.Arg67Cys
Coding: c.199C>T
MANE Select: NM_080283
Type: single nucleotide variant
Location: chr17:69049388 (GRCh38)
Gene constraint: LOEUF 1.006 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.22

Full ABCA9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA9 p.Arg67Gly Uncertain significance ★ ⚠ same residue
ABCA9 p.Tyr1123= Likely benign ★★ same type
ABCA9 p.Ala1071Val Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1153Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1196Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala125Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1285Thr Uncertain significance ★ ⚠ same type
ABCA9 p.Ala1407Val 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/abca9-p-arg67cys (accessed [today's date]).

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