Is ABCA12 p.Val925Ile (c.2773G>A) pathogenic?

ABCA12 p.Val925Ile (c.2773G>A) is classified Conflicting classifications of pathogenicity in ABCA12 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-20). AlphaMissense: likely benign (0.0604); Ultra-rare (popmax 0.0534%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCA12 p.Val925Ile (c.2773G>A)?

ABCA12 p.Val925Ile (c.2773G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCA12 p.Val925Ile (c.2773G>A) in the general population?

ABCA12 p.Val925Ile (c.2773G>A) is ultra-rare (popmax 0.0534%, afr) (gnomAD).

What do computational predictors say about ABCA12 p.Val925Ile (c.2773G>A)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

ABCA12 p.Val925Ile

c.2773G>A · rs141142206 · VCV2718483

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0534%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.266	benign-leaning
SaProt	LLR -6.11	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 1.1	GERP 0.51, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 85 kb · p 1.7e-09 · regional, not allelic
Overall
CADD	15.36	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 0.0534% African / African-American · 40/74,876 alleles

Filtering AF 0.0402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0357%

Overall 0.00316% 51/1,613,576 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0534%	1,872
Admixed American	0.0133%	7,497
Remaining individualsnot grpmax-eligible	0.0032%	31,237
European (non-Finnish)	8.48e-05%	1,179,824

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.Val925Ile
Coding: c.2773G>A
MANE Select: NM_173076
dbSNP: rs141142206
Type: single nucleotide variant
Location: chr2:215001648 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 925: a UniProt-annotated variant site (in arci4b)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA12 p.Ala134Ser Uncertain significance ★★ ⚠ same condition
ABCA12 p.Ala51Glu Uncertain significance ★★ ⚠ same condition
ABCA12 p.Ala833Val Uncertain significance ★★ ⚠ same condition
ABCA12 p.Arg1417Trp Uncertain significance ★★ ⚠ same condition
ABCA12 p.Arg1950Gln Uncertain significance ★★ ⚠ same condition
ABCA12 p.Asp505Val Uncertain significance ★★ ⚠ same condition
ABCA12 p.Asp756Val Uncertain significance ★★ ⚠ same condition
ABCA12 p.Gly2305Arg Uncertain significance ★★ ⚠ same condition

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-val925ile (accessed [today's date]).

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