Is PIGN p.His153= (c.459C>T) pathogenic?

PIGN p.His153= (c.459C>T) is classified Benign/Likely benign in PIGN (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-01). Rare (popmax 0.145%, afr); Associated with Inborn genetic diseases.

What condition is associated with PIGN p.His153= (c.459C>T)?

PIGN p.His153= (c.459C>T) is associated with Inborn genetic diseases, multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

How common is PIGN p.His153= (c.459C>T) in the general population?

PIGN p.His153= (c.459C>T) is rare (popmax 0.145%, afr) (gnomAD).

PIGN p.His153=

c.459C>T · rs376615257 · VCV472231

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.145%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.2	GERP -1.9, phastCons 0.68
Overall
CADD	9.182	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.145% African / African-American · 106/73,208 alleles

Filtering AF 0.122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00955% 147/1,540,026 alleles · rare exomes 87/1,388,054 · genomes 60/151,972 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.145%	691
Middle Eastern	0.0337%	2,970
Admixed American	0.0286%	3,494
Remaining individualsnot grpmax-eligible	0.00835%	11,974
South Asian	0.00452%	22,122
East Asian	0.00225%	44,410
European (non-Finnish)	0.00108%	93,015

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.His153=
Coding: c.459C>T
MANE Select: NM_176787
dbSNP: rs376615257
Type: single nucleotide variant
Location: chr18:62154635 (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 p.His153Tyr Uncertain significance ★ ⚠ same residue
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

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-his153 (accessed [today's date]).

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