Is ABCA2 p.Phe1690Val (c.5068T>G) pathogenic?

ABCA2 p.Phe1690Val (c.5068T>G) is classified Uncertain significance in ABCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-19). AlphaMissense: ambiguous (0.5426); Very rare (popmax 0.01%, amr); Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

How common is ABCA2 p.Phe1690Val (c.5068T>G) in the general population?

ABCA2 p.Phe1690Val (c.5068T>G) is very rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about ABCA2 p.Phe1690Val (c.5068T>G)?

AlphaMissense predicts ambiguous (score 0.5426) — an in-silico prediction, not a clinical call.

ABCA2 p.Phe1690Val

Q: What condition is associated with ABCA2 p.Phe1690Val (c.5068T>G)?

ABCA2 p.Phe1690Val (c.5068T>G) is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

c.5068T>G · rs769560287 · VCV2441927

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.01%, amr)

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.5426	ambiguous
REVEL	0.596	indeterminate
SaProt	LLR -4.72	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 3,800 bp · p 6.1e-23 · regional, not allelic
Overall
CADD	23.9	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 F1689V vs ClinVar F1690V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/60,004 alleles

Filtering AF 0.00428% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000411% 6/1,460,240 alleles · very rare

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.Phe1690Val
Coding: c.5068T>G
MANE Select: NM_001606
dbSNP: rs769560287
Type: single nucleotide variant
Location: chr9:137012725 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1690: 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-phe1690val (accessed [today's date]).

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