Is ABCA4 p.Leu1940Pro (c.5819T>C) pathogenic?

ABCA4 p.Leu1940Pro (c.5819T>C) is classified Pathogenic/Likely pathogenic in ABCA4 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-09-10). AlphaMissense: likely pathogenic (0.9723); Very rare (popmax 0.00833%, amr); Associated with ABCA4-related disorder.

What condition is associated with ABCA4 p.Leu1940Pro (c.5819T>C)?

ABCA4 p.Leu1940Pro (c.5819T>C) is associated with ABCA4-related disorder, severe early-childhood-onset retinal dystrophy, cone-rod dystrophy 3 (ClinVar).

How common is ABCA4 p.Leu1940Pro (c.5819T>C) in the general population?

ABCA4 p.Leu1940Pro (c.5819T>C) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about ABCA4 p.Leu1940Pro (c.5819T>C)?

AlphaMissense predicts likely pathogenic (score 0.9723) — an in-silico prediction, not a clinical call.

ABCA4 p.Leu1940Pro

c.5819T>C · rs61753033 · VCV7911

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely pathogenic

0.9723 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA4-related disorder

Computational evidence

Protein change
AlphaMissense	0.9723	likely pathogenic ✓ concordant with ClinVar · top 3% in ABCA4
REVEL	0.85	moderately pathogenic-leaning
SaProt	LLR -14.69	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 128 kb · p 0.24 · regional, not allelic
Overall
CADD	27.4	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 0.00833% Admixed American · 5/60,030 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00206%

Overall 0.000684% 10/1,461,856 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,006
African / African-American	0.00133%	75,006
European (non-Finnish)	0.000339%	295,002

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.Leu1940Pro
Coding: c.5819T>C
MANE Select: NM_000350
dbSNP: rs61753033
Type: single nucleotide variant
Location: chr1:94008767 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1940: 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); a UniProt-annotated variant site (found in a patient with macular dystrophy; uncertain significance); the abc transporter 2 domain; a UniProt-annotated variant site (in stgd1 and cord3; uncertain significance); a UniProt-annotated variant site (sequence variant); a UniProt-annotated variant site (in stgd1 and ffm; uncertain significance); a UniProt-annotated variant site (in stgd1 and ffm); a β-strand

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

Disease context

Also linked: severe early-childhood-onset retinal dystrophy cone-rod dystrophy 3 Stargardt disease

Similar variants

ABCA4 p.Leu1940Gln Likely pathogenic ★ same residue
ABCA4 p.Leu1940Ile Uncertain significance ★ ⚠ same residue
ABCA4 p.Leu1940= Likely benign ★ 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

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-leu1940pro (accessed [today's date]).

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