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

SCAPER p.Met1Val (c.1A>G) is classified Benign in SCAPER (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-11-07). Common (popmax 53.2%, eas) — too common for a highly-penetrant pathogenic allele; Associated with intellectual developmental disorder and retinitis pigmentosa; IDDRP.

What condition is associated with SCAPER p.Met1Val (c.1A>G)?

SCAPER p.Met1Val (c.1A>G) is associated with intellectual developmental disorder and retinitis pigmentosa; IDDRP (ClinVar).

SCAPER p.Met1Val

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

SCAPER p.Met1Val (c.1A>G) is common (popmax 53.2%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1A>G · rs3812908 · VCV1327986

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

start-loss

predicted LoF

gnomAD v4.1

Common

common (popmax 53.2%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual developmental disorder and retinitis pigmentosa; IDDRP

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	0.215	benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 1.7, phastCons 1
Overall
CADD	18.57	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 53.2% East Asian · 21,772/40,948 alleles

Filtering AF 52.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.3%

Overall 30.1% 444,024/1,476,434 alleles · common exomes 393,753/1,324,358 · genomes 50,271/152,076 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	53.2%	2
South Asian	47.5%	2
Amishnot grpmax-eligible	41.1%	2
Ashkenazi Jewishnot grpmax-eligible	34.2%	3
Remaining individualsnot grpmax-eligible	31.8%	3
African / African-American	31.3%	3
Finnishnot grpmax-eligible	31%	3
Admixed American	30.9%	3
Middle Eastern	29.7%	3
European (non-Finnish)	27.6%	4

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: SCAPER
Protein: p.Met1Val
Coding: c.1A>G
MANE Select: NM_020843
dbSNP: rs3812908
Type: single nucleotide variant
Location: chr15:76883817 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.35 · 2 PDB

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

Disease context

intellectual developmental disorder and retinitis pigmentosa; IDDRP — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SCAPER p.Arg112Ter Likely pathogenic ★★ same condition
SCAPER p.Lys869Ter Pathogenic/Likely pathogenic ★★ same condition
SCAPER c.2645+36T>C Benign ★★ same condition
SCAPER c.3078+39G>T Benign ★★ same condition
SCAPER c.3705+3A>G Benign ★★ same condition
SCAPER c.612-4A>G Benign ★★ same condition
SCAPER c.772+1881G>T Benign ★★ same condition
SCAPER c.-42T>A Benign ★★ 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/scaper-p-met1val (accessed [today's date]).

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