Is ABCA4 p.Ser206= (c.618C>T) pathogenic?

ABCA4 p.Ser206= (c.618C>T) is classified Conflicting classifications of pathogenicity in ABCA4 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-22). Low-frequency (popmax 1.06%, afr); Associated with Inborn genetic diseases.

What condition is associated with ABCA4 p.Ser206= (c.618C>T)?

ABCA4 p.Ser206= (c.618C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABCA4 p.Ser206= (c.618C>T) in the general population?

ABCA4 p.Ser206= (c.618C>T) is low-frequency (popmax 1.06%, afr) (gnomAD).

ABCA4 p.Ser206=

c.618C>T · rs61748536 · VCV377401

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.06%, afr)

Conditions

Inborn genetic diseases

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 -2.7	GERP -3.8
Overall
CADD	3.492	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.06% African / African-American · 799/75,040 alleles

Filtering AF 1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.979%

Overall 0.0538% 868/1,612,626 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.06%	94
Admixed American	0.0416%	2,401
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Middle Eastern	0.033%	3,031
South Asian	0.00549%	18,215
East Asian	0.00223%	44,868
European (non-Finnish)	0.000847%	118,001

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.Ser206=
Coding: c.618C>T
MANE Select: NM_000350
dbSNP: rs61748536
Type: single nucleotide variant
Location: chr1:94098944 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.96 · 8 PDB
Residue 206: a UniProt-annotated variant site (in cord3; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance); a UniProt-annotated variant site (in stgd1; uncertain significance; reduced basal and retinal-stimulated atp-hydrolysis); a disulfide bond

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA4 p.Ser206Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCA4 p.Ala1287Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala1324Val Uncertain significance ★★ ⚠ same condition
ABCA4 p.Ala45Gly Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1170Thr Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg140Pro Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg1963His Uncertain significance ★★ ⚠ same condition
ABCA4 p.Arg487Pro Uncertain significance ★★ ⚠ 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-ser206 (accessed [today's date]).

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