Is ABCA10 p.Phe1488Val (c.4462T>G) pathogenic?

ABCA10 p.Phe1488Val (c.4462T>G) is classified Uncertain significance in ABCA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.0901); Very rare (popmax 0.00668%, amr).

How common is ABCA10 p.Phe1488Val (c.4462T>G) in the general population?

ABCA10 p.Phe1488Val (c.4462T>G) is very rare (popmax 0.00668%, amr) (gnomAD).

What do computational predictors say about ABCA10 p.Phe1488Val (c.4462T>G)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

ABCA10 p.Phe1488Val

c.4462T>G · VCV3836228

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.189	benign-leaning
SaProt	LLR -4.55	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 0.028	GERP -3.5
Regional constraint	o/e 0.95	unconstrained · MANE · 77 kb · p 0.045 · regional, not allelic
Overall
CADD	9.632	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 0.00668% Admixed American · 4/59,888 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,460,044 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: ABCA10
Protein: p.Phe1488Val
Coding: c.4462T>G
MANE Select: NM_001377321
Type: single nucleotide variant
Location: chr17:69149999 (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-phe1488val (accessed [today's date]).

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