Is CD59 p.Met1Val (c.1A>G) pathogenic?

CD59 p.Met1Val (c.1A>G) is classified Uncertain significance in CD59 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-30). Very rare (popmax 0.00288%, nfe).

How common is CD59 p.Met1Val (c.1A>G) in the general population?

CD59 p.Met1Val (c.1A>G) is very rare (popmax 0.00288%, nfe) (gnomAD).

CD59 p.Met1Val

c.1A>G · rs368463258 · VCV1972055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

start-loss

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00288%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	start-loss	predicted loss-of-function
REVEL	0.743	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.2, phastCons 1
Overall
CADD	20.9	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 0.00288% European (non-Finnish) · 34/1,179,786 alleles

Filtering AF 0.00207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00239% 35/1,461,520 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00288%	34,700
Admixed American	0.00167%	59,996

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: CD59
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_000611
dbSNP: rs368463258
Type: single nucleotide variant
Location: chr11:33722445 (GRCh38)
Gene constraint: LOEUF 1.277 · pLI 0.57 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.15 · 17 PDB

Full CD59 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD59 p.Met1Thr Likely pathogenic ★★ same residue
CD59 p.Cys89Tyr Pathogenic ★★ same type
CD59 p.Ala50Val Uncertain significance ★★ ⚠ same type
CD59 p.Arg78Cys Uncertain significance ★★ ⚠ same type
CD59 p.Asn33Thr Uncertain significance ★★ ⚠ same type
CD59 p.Asp92Asn Uncertain significance ★★ ⚠ same type
CD59 p.Thr105Pro Uncertain significance ★★ ⚠ same type
CD59 p.Val18Ile 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/cd59-p-met1val (accessed [today's date]).

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