Is ABCA2 p.Met1Val (c.1A>G) pathogenic?

ABCA2 p.Met1Val (c.1A>G) is classified Benign in ABCA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2018-07-13). Low-frequency (popmax 4.21%, afr).

How common is ABCA2 p.Met1Val (c.1A>G) in the general population?

ABCA2 p.Met1Val (c.1A>G) is low-frequency (popmax 4.21%, afr) (gnomAD).

ABCA2 p.Met1Val

c.1A>G · rs142807525 · VCV785303

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 4.21%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function in a LoF-intolerant gene
REVEL	0.018	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.4	GERP -1.1
Overall
CADD	2.104	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.21% African / African-American · 2,722/64,604 alleles

Filtering AF 4.08% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.03%

Overall 0.225% 2,993/1,328,010 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.21%	24
Admixed American	0.241%	414
Remaining individualsnot grpmax-eligible	0.231%	432
Middle Eastern	0.0642%	1,557
South Asian	0.0133%	7,509
European (non-Finnish)	0.00418%	23,950

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.Met1Val
Coding: c.1A>G
MANE Select: NM_001606 · reported on NM_212533
dbSNP: rs142807525
Type: single nucleotide variant
Location: chr9:137028872 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46

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-met1val (accessed [today's date]).

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