Is ABCA8 p.Ala809Val (c.2426C>T) pathogenic?

ABCA8 p.Ala809Val (c.2426C>T) is classified Benign in ABCA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-01). AlphaMissense: likely benign (0.0673); Low-frequency (popmax 1.17%, sas).

How common is ABCA8 p.Ala809Val (c.2426C>T) in the general population?

ABCA8 p.Ala809Val (c.2426C>T) is low-frequency (popmax 1.17%, sas) (gnomAD).

What do computational predictors say about ABCA8 p.Ala809Val (c.2426C>T)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

ABCA8 p.Ala809Val

c.2426C>T · VCV3770620

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.17%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.37	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 -6.3	GERP -4.1
Regional constraint	o/e 1.01	unconstrained · MANE · 74 kb · p 0.82 · regional, not allelic
Overall
CADD	0.251	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 1.17% South Asian · 1,062/91,062 alleles

Filtering AF 1.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.08%

Overall 0.101% 1,636/1,613,900 alleles · low-frequency exomes 1,517/1,461,858 · genomes 119/152,042 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.17%	86
Middle Eastern	0.627%	160
Remaining individualsnot grpmax-eligible	0.163%	613
Admixed American	0.0483%	2,069
European (non-Finnish)	0.0334%	2,995
Ashkenazi Jewishnot grpmax-eligible	0.0237%	4,228
African / African-American	0.004%	24,985
East Asian	0.00223%	44,860

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: ABCA8
Protein: p.Ala809Val
Coding: c.2426C>T
MANE Select: NM_001288985
Type: single nucleotide variant
Location: chr17:68903472 (GRCh38)
Gene constraint: LOEUF 1.086 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.67
Residue 809: a UniProt-annotated variant site (loss of expression; loss of cholesterol efflux to apoa1)

Full ABCA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA8 p.Gly176Ser Uncertain significance ★★ ⚠ same type
ABCA8 c.4200-1G>C Benign ★★ same type
ABCA8 p.Gly1225Glu Benign ★★ same type
ABCA8 p.Ile542= Benign/Likely benign ★★ same type
ABCA8 p.Met251Ile Benign ★★ same type
ABCA8 c.3316-8G>T Uncertain significance ★ same type
ABCA8 p.Ala1109Val Uncertain significance ★ ⚠ same type
ABCA8 p.Ala1344Ser 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/abca8-p-ala809val (accessed [today's date]).

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