Is ABCA4 p.Phe1440= (c.4320T>C) pathogenic?

ABCA4 p.Phe1440= (c.4320T>C) is classified Likely benign in ABCA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-19). Very rare (popmax 8.47e-05%, nfe).

How common is ABCA4 p.Phe1440= (c.4320T>C) in the general population?

ABCA4 p.Phe1440= (c.4320T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ABCA4 p.Phe1440=

c.4320T>C · rs2101034937 · VCV1106831

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.004	GERP -3.5, phastCons 0.021
Overall
CADD	6.288	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,878 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: ABCA4
Protein: p.Phe1440=
Coding: c.4320T>C
MANE Select: NM_000350
dbSNP: rs2101034937
Type: single nucleotide variant
Location: chr1:94030460 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 1440: 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); a UniProt-annotated variant site (in stgd1); a β-strand; a disulfide bond

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

Similar variants

ABCA4 p.Phe1440Val Likely pathogenic ★★ ⚠ same residue
ABCA4 p.Phe1440Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 p.Phe1440fs Pathogenic ★ 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

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-phe1440 (accessed [today's date]).

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