Is ABCA4 p.Ala626= (c.1878G>A) pathogenic?

ABCA4 p.Ala626= (c.1878G>A) is classified Benign/Likely benign in ABCA4 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-26). Low-frequency (popmax 1.08%, afr); Associated with severe early-childhood-onset retinal dystrophy.

What condition is associated with ABCA4 p.Ala626= (c.1878G>A)?

ABCA4 p.Ala626= (c.1878G>A) is associated with severe early-childhood-onset retinal dystrophy, age related macular degeneration 2, retinitis pigmentosa 19 (ClinVar).

How common is ABCA4 p.Ala626= (c.1878G>A) in the general population?

ABCA4 p.Ala626= (c.1878G>A) is low-frequency (popmax 1.08%, afr) (gnomAD).

How is Severe early-childhood-onset retinal dystrophy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ABCA4 p.Ala626=

c.1878G>A · rs61754023 · VCV99093

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.08%, afr)

Conditions

severe early-childhood-onset retinal dystrophy

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 -1.6	GERP -3.9
Overall
CADD	0.796	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.08% African / African-American · 809/75,036 alleles

Filtering AF 1.02% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.992%

Overall 0.0609% 983/1,614,168 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.08%	93
Remaining individualsnot grpmax-eligible	0.0704%	1,421
Admixed American	0.0583%	1,715
Middle Eastern	0.0495%	2,021
South Asian	0.011%	9,109
East Asian	0.00669%	14,959
European (non-Finnish)	0.00661%	15,129
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Ala626=
Coding: c.1878G>A
MANE Select: NM_000350
dbSNP: rs61754023
Type: single nucleotide variant
Location: chr1:94062636 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 626: a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (found in a patient with chorioretinal atrophy; uncertain significance)

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

Disease context

severe early-childhood-onset retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: age related macular degeneration 2 retinitis pigmentosa 19 cone-rod dystrophy 3

For Severe early-childhood-onset retinal dystrophy (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

ABCA4 p.Ala626Val Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 c.1937+1G>A Pathogenic ★★★ same condition
ABCA4 c.3523-1G>A Pathogenic ★★★ same condition
ABCA4 c.4253+43G>A Pathogenic ★★★ same condition
ABCA4 c.4254-1G>C Pathogenic ★★★ same condition
ABCA4 c.4352+1G>A Pathogenic ★★★ same condition
ABCA4 c.4773+3A>G Pathogenic ★★★ same condition
ABCA4 c.5018+2T>C Pathogenic ★★★ 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/abca4-p-ala626 (accessed [today's date]).

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