Is ABCA2 p.Ala465Val (c.1394C>T) pathogenic?

ABCA2 p.Ala465Val (c.1394C>T) is classified Conflicting classifications of pathogenicity in ABCA2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-04-20). AlphaMissense: likely benign (0.0655); Rare (popmax 0.123%, nfe); Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

How common is ABCA2 p.Ala465Val (c.1394C>T) in the general population?

ABCA2 p.Ala465Val (c.1394C>T) is rare (popmax 0.123%, nfe) (gnomAD).

What do computational predictors say about ABCA2 p.Ala465Val (c.1394C>T)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

ABCA2 p.Ala465Val

Q: What condition is associated with ABCA2 p.Ala465Val (c.1394C>T)?

ABCA2 p.Ala465Val (c.1394C>T) is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

c.1394C>T · VCV3779316

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.123%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual developmental disorder with poor growth and with or without seizures or ataxia

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -4.84	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 1.1, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,539 bp · p 6.3e-06 · regional, not allelic
Overall
CADD	17.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A464V vs ClinVar A465V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.123% European (non-Finnish) · 1,456/1,179,976 alleles

Filtering AF 0.118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.116%

Overall 0.0975% 1,573/1,612,960 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.123%	810
Amishnot grpmax-eligible	0.11%	912
Remaining individualsnot grpmax-eligible	0.088%	1,136
Admixed American	0.0383%	2,610
Finnishnot grpmax-eligible	0.0366%	2,735
African / African-American	0.0173%	5,774
Middle Eastern	0.0166%	6,038
East Asian	0.00223%	44,882

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.Ala465Val
Coding: c.1394C>T
MANE Select: NM_001606
Type: single nucleotide variant
Location: chr9:137020367 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 465: a UniProt-annotated variant site (in idpogsa)

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

Disease context

intellectual developmental disorder with poor growth and with or without seizures or ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg114Gln Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1160His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1383His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1664Trp Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg954His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Asn1755Lys 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/abca2-p-ala465val (accessed [today's date]).

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