Is ABCA1 p.Phe1854= (c.5562C>T) pathogenic?

ABCA1 p.Phe1854= (c.5562C>T) is classified Likely benign in ABCA1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-05). Very rare (popmax 0.00559%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ABCA1 p.Phe1854= (c.5562C>T)?

ABCA1 p.Phe1854= (c.5562C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ABCA1 p.Phe1854= (c.5562C>T) in the general population?

ABCA1 p.Phe1854= (c.5562C>T) is very rare (popmax 0.00559%, nfe) (gnomAD).

ABCA1 p.Phe1854=

c.5562C>T · rs368105002 · VCV1748319

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00559%, nfe)

Conditions

Cardiovascular phenotype

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 -6.4	GERP -4.2
Overall
CADD	1.04	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00559% European (non-Finnish) · 66/1,180,014 alleles

Filtering AF 0.00451% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00411%

Overall 0.00452% 73/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00559%	17,879
African / African-American	0.00401%	24,959
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00312%	32,015
Admixed American	0.00167%	59,992

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: ABCA1
Protein: p.Phe1854=
Coding: c.5562C>T
MANE Select: NM_005502
dbSNP: rs368105002
Type: single nucleotide variant
Location: chr9:104793245 (GRCh38)
Gene constraint: LOEUF 0.563 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.50 · 7 PDB
Residue 1854: an α-helix

Full ABCA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA1 c.4175+1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCA1 p.Thr940Met Pathogenic/Likely pathogenic ★★ same condition
ABCA1 c.3787+5C>A Uncertain significance ★★ same condition
ABCA1 p.Ala1855Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Ala766Ser Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1283Cys Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1342Trp Uncertain significance ★★ ⚠ same condition
ABCA1 p.Arg1417Cys 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/abca1-p-phe1854 (accessed [today's date]).

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