Is ABCA10 p.Ile783Thr (c.2348T>C) pathogenic?

ABCA10 p.Ile783Thr (c.2348T>C) is classified Uncertain significance in ABCA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely benign (0.1312); Ultra-rare (popmax 0.0588%, afr).

How common is ABCA10 p.Ile783Thr (c.2348T>C) in the general population?

ABCA10 p.Ile783Thr (c.2348T>C) is ultra-rare (popmax 0.0588%, afr) (gnomAD).

What do computational predictors say about ABCA10 p.Ile783Thr (c.2348T>C)?

AlphaMissense predicts likely benign (score 0.1312) — an in-silico prediction, not a clinical call.

ABCA10 p.Ile783Thr

c.2348T>C · rs150316122 · VCV2383989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1312 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0588%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1312	likely benign
REVEL	0.328	indeterminate
SaProt	LLR -8.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.9, phastCons 0.024
Regional constraint	o/e 0.95	unconstrained · MANE · 77 kb · p 0.045 · regional, not allelic
Overall
CADD	18.83	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 0.0588% African / African-American · 44/74,840 alleles

Filtering AF 0.0449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.00342% 55/1,606,720 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0588%	1,701
Admixed American	0.00845%	11,830
East Asian	0.00223%	44,800
Remaining individualsnot grpmax-eligible	0.00161%	62,134
South Asian	0.00111%	90,160
European (non-Finnish)	0.000255%	391,906

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: ABCA10
Protein: p.Ile783Thr
Coding: c.2348T>C
MANE Select: NM_001377321
dbSNP: rs150316122
Type: single nucleotide variant
Location: chr17:69185626 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.70

Full ABCA10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA10 p.Ala1181Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1187Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1307Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1335Pro Uncertain significance ★ ⚠ same type
ABCA10 p.Ala1461Thr Uncertain significance ★ ⚠ same type
ABCA10 p.Ala244Ser Uncertain significance ★ ⚠ same type
ABCA10 p.Ala424Val Uncertain significance ★ ⚠ same type
ABCA10 p.Ala749Val 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/abca10-p-ile783thr (accessed [today's date]).

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