Is PIGN p.Asp415= (c.1245T>C) pathogenic?

PIGN p.Asp415= (c.1245T>C) is classified Benign in PIGN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 24.7%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with PIGN p.Asp415= (c.1245T>C)?

PIGN p.Asp415= (c.1245T>C) is associated with Inborn genetic diseases, multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

PIGN p.Asp415=

Q: How common is PIGN p.Asp415= (c.1245T>C) in the general population?

PIGN p.Asp415= (c.1245T>C) is common (popmax 24.7%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1245T>C · rs13381627 · VCV403304

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 24.7%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Inborn genetic diseases

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 -0.5	GERP -3.5
Overall
CADD	0.238	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 24.7% European (non-Finnish) · 272,684/1,105,280 alleles

Filtering AF 24.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 24.6%

Overall 21.7% 326,589/1,505,156 alleles · common exomes 300,647/1,353,106 · genomes 25,942/152,050 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	24.9%	4
Ashkenazi Jewishnot grpmax-eligible	24.7%	4
European (non-Finnish)grpmax	24.7%	4
Middle Eastern	24.2%	4
Finnishnot grpmax-eligible	23.7%	4
Remaining individualsnot grpmax-eligible	20.4%	5
Admixed American	12.7%	8
South Asian	11.3%	9
African / African-American	4.63%	22
East Asian	0.182%	551

Amish 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: PIGN
Protein: p.Asp415=
Coding: c.1245T>C
MANE Select: NM_176787
dbSNP: rs13381627
Type: single nucleotide variant
Location: chr18:62114567 (GRCh38)
Gene constraint: LOEUF 1.46 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 88.33

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple congenital anomalies-hypotonia-seizures syndrome 1

Similar variants

PIGN c.1251+1G>A Pathogenic/Likely pathogenic ★★ same condition
PIGN c.1252-2A>G Pathogenic/Likely pathogenic ★★ same condition
PIGN c.1434+5G>A Pathogenic/Likely pathogenic ★★ same condition
PIGN c.1574+1G>A Likely pathogenic ★★ same condition
PIGN c.1674+1G>A Likely pathogenic ★★ same condition
PIGN c.1674+1G>C Pathogenic ★★ same condition
PIGN c.1675-1G>T Pathogenic/Likely pathogenic ★★ same condition
PIGN c.222-1G>A Likely pathogenic ★★ 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/pign-p-asp415 (accessed [today's date]).

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