Is PIGN p.Ala103= (c.309T>C) pathogenic?

PIGN p.Ala103= (c.309T>C) is classified Benign in PIGN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-03). Common (popmax 5.52%, amr) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with PIGN p.Ala103= (c.309T>C)?

PIGN p.Ala103= (c.309T>C) is associated with Inborn genetic diseases, multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

PIGN p.Ala103=

Q: How common is PIGN p.Ala103= (c.309T>C) in the general population?

PIGN p.Ala103= (c.309T>C) is common (popmax 5.52%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.309T>C · rs17069511 · VCV472230

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 5.52%, amr) — 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 -0.23	GERP -3.6, phastCons 0.003
Overall
CADD	4.855	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.52% Admixed American · 3,300/59,752 alleles

Filtering AF 5.37% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.3%

Overall 0.246% 3,964/1,612,106 alleles · common exomes 3,392/1,459,762 · genomes 572/152,344 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	5.52%	18
East Asian	1.09%	92
Remaining individualsnot grpmax-eligible	0.149%	671
African / African-American	0.0626%	1,597
Middle Eastern	0.0165%	6,062
South Asian	0.00552%	18,112
European (non-Finnish)	0.00254%	39,300

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.Ala103=
Coding: c.309T>C
MANE Select: NM_176787
dbSNP: rs17069511
Type: single nucleotide variant
Location: chr18:62157721 (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-ala103 (accessed [today's date]).

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