Is ABCA10 p.Phe40Leu (c.118T>C) pathogenic?

ABCA10 p.Phe40Leu (c.118T>C) is classified Uncertain significance in ABCA10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely pathogenic (0.945); Very rare (popmax 0.00353%, amr).

How common is ABCA10 p.Phe40Leu (c.118T>C) in the general population?

ABCA10 p.Phe40Leu (c.118T>C) is very rare (popmax 0.00353%, amr) (gnomAD).

What do computational predictors say about ABCA10 p.Phe40Leu (c.118T>C)?

AlphaMissense predicts likely pathogenic (score 0.945) — an in-silico prediction, not a clinical call.

ABCA10 p.Phe40Leu

c.118T>C · VCV4830770

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.945 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00353%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.945	likely pathogenic · top 1% in ABCA10
REVEL	0.444	indeterminate
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 77 kb · p 0.045 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00353% Admixed American · 2/56,592 alleles

Filtering AF 0.000586% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000219%

Overall 0.000413% 6/1,451,428 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00353%	28,296
European (non-Finnish)	0.00034%	294,446

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.Phe40Leu
Coding: c.118T>C
MANE Select: NM_001377321
Type: single nucleotide variant
Location: chr17:69222614 (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-phe40leu (accessed [today's date]).

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