Is ABCA4 p.Ala45= (c.135C>T) pathogenic?

ABCA4 p.Ala45= (c.135C>T) is classified Likely benign in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-05). Very rare (popmax 0.005%, amr).

How common is ABCA4 p.Ala45= (c.135C>T) in the general population?

ABCA4 p.Ala45= (c.135C>T) is very rare (popmax 0.005%, amr) (gnomAD).

ABCA4 p.Ala45=

c.135C>T · rs768633039 · VCV2135272

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.1, phastCons 1
Overall
CADD	12.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,018 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000372% 6/1,613,934 alleles · very rare exomes 6/1,461,726 · genomes 0/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,006
African / African-American	0.00267%	37,496
Remaining individualsnot grpmax-eligible	0.0016%	62,494

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: ABCA4
Protein: p.Ala45=
Coding: c.135C>T
MANE Select: NM_000350
dbSNP: rs768633039
Type: single nucleotide variant
Location: chr1:94112998 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 45: a UniProt-annotated variant site (in stgd1; uncertain significance)

Full ABCA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA4 p.Ala45Gly Uncertain significance ★★ ⚠ same residue
ABCA4 p.Ala45Val Uncertain significance ★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same type
ABCA4 c.3328+2T>A Pathogenic ★★★ same type
ABCA4 c.3523-1G>A Pathogenic ★★★ same type
ABCA4 c.4253+43G>A Pathogenic ★★★ same type
ABCA4 c.4254-1G>C Pathogenic ★★★ same type
ABCA4 c.4352+1G>A Pathogenic ★★★ 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/abca4-p-ala45 (accessed [today's date]).

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