Is ABCA2 p.Ala1645Val (c.4934C>T) pathogenic?

ABCA2 p.Ala1645Val (c.4934C>T) is classified Uncertain significance in ABCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-14). AlphaMissense: likely benign (0.0702); Ultra-rare (popmax 0.0188%, sas).

How common is ABCA2 p.Ala1645Val (c.4934C>T) in the general population?

ABCA2 p.Ala1645Val (c.4934C>T) is ultra-rare (popmax 0.0188%, sas) (gnomAD).

What do computational predictors say about ABCA2 p.Ala1645Val (c.4934C>T)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

ABCA2 p.Ala1645Val

c.4934C>T · rs762067339 · VCV2378133

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -7.36	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP 1.5, phastCons 0.026
Regional constraint	o/e 0.93	unconstrained · MANE · 629 bp · p 0.29 · regional, not allelic
Overall
CADD	19.49	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A1644V vs ClinVar A1645V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0188% South Asian · 17/90,296 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00984%

Overall 0.00836% 134/1,602,600 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0188%	5,312
Middle Eastern	0.0168%	5,956
Remaining individualsnot grpmax-eligible	0.0113%	8,848
European (non-Finnish)	0.00911%	10,972
East Asian	0.00224%	44,592
African / African-American	0.00134%	74,838

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: ABCA2
Protein: p.Ala1645Val
Coding: c.4934C>T
MANE Select: NM_001606
dbSNP: rs762067339
Type: single nucleotide variant
Location: chr9:137012859 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1645: a UniProt-annotated variant site (in idpogsa)

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same type
ABCA2 c.3883-3C>T Uncertain significance ★★ same type
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1620Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1715Ser Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2180Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2206Val Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala322Val 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/abca2-p-ala1645val (accessed [today's date]).

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