Is ABCA12 p.Ser428Thr (c.1282T>A) pathogenic?

ABCA12 p.Ser428Thr (c.1282T>A) is classified Benign in ABCA12 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). AlphaMissense: likely benign (0.0991); Ultra-rare (popmax 0.0766%, afr).

How common is ABCA12 p.Ser428Thr (c.1282T>A) in the general population?

ABCA12 p.Ser428Thr (c.1282T>A) is ultra-rare (popmax 0.0766%, afr) (gnomAD).

What do computational predictors say about ABCA12 p.Ser428Thr (c.1282T>A)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

ABCA12 p.Ser428Thr

c.1282T>A · rs112586692 · VCV2713259

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0766%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -6.66	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 6.1	GERP -0.29, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 94 kb · p 0.48 · regional, not allelic
Overall
CADD	17.58	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 0.0766% African / African-American · 48/62,628 alleles

Filtering AF 0.0593% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0532%

Overall 0.00619% 93/1,501,584 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0766%	1,305
Remaining individualsnot grpmax-eligible	0.0618%	1,617
Admixed American	0.00396%	25,236
Finnishnot grpmax-eligible	0.00179%	55,990
European (non-Finnish)	0.000533%	187,480

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: ABCA12
Protein: p.Ser428Thr
Coding: c.1282T>A
MANE Select: NM_173076
dbSNP: rs112586692
Type: single nucleotide variant
Location: chr2:215025678 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32

Full ABCA12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA12 c.2592+1G>A Likely pathogenic ★★ same type
ABCA12 c.5381+1G>C Pathogenic/Likely pathogenic ★★ same type
ABCA12 c.985+1G>A Likely pathogenic ★★ same type
ABCA12 p.Arg1297Ter Pathogenic ★★ same type
ABCA12 p.Arg1514Cys Pathogenic ★★ same type
ABCA12 p.Arg1514His Pathogenic/Likely pathogenic ★★ same type
ABCA12 p.Arg1515Ter Pathogenic ★★ same type
ABCA12 p.Arg1950Ter Pathogenic ★★ 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/abca12-p-ser428thr (accessed [today's date]).

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