Is ABCA2 p.Pro357= (c.1071C>T) pathogenic?

ABCA2 p.Pro357= (c.1071C>T) is classified Likely benign in ABCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-01). Rare (popmax 0.224%, sas).

How common is ABCA2 p.Pro357= (c.1071C>T) in the general population?

ABCA2 p.Pro357= (c.1071C>T) is rare (popmax 0.224%, sas) (gnomAD).

ABCA2 p.Pro357=

c.1071C>T · rs199700897 · VCV1695276

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.224%, sas)

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 -14	GERP -2.3
Overall
CADD	0.031	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.224% South Asian · 189/84,394 alleles

Filtering AF 0.207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.204%

Overall 0.224% 3,478/1,549,416 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.17%	85
South Asiangrpmax	0.224%	447
European (non-Finnish)	0.214%	467
Remaining individualsnot grpmax-eligible	0.185%	540
African / African-American	0.0327%	3,062
Ashkenazi Jewishnot grpmax-eligible	0.0247%	4,046
Middle Eastern	0.0169%	5,926
Admixed American	0.012%	8,360
East Asian	0.0048%	20,851

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABCA2
Protein: p.Pro357=
Coding: c.1071C>T
MANE Select: NM_001606
dbSNP: rs199700897
Type: single nucleotide variant
Location: chr9:137020888 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 357: a UniProt-annotated variant site (in idpogsa)

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same type
ABCA2 c.3883-3C>T Uncertain significance ★★ same type
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1620Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1645Val Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1715Ser Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2180Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2206Val Uncertain significance ★★ ⚠ 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/abca2-p-pro357 (accessed [today's date]).

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