Is PIGN p.Arg95Trp (c.283C>T) pathogenic?

PIGN p.Arg95Trp (c.283C>T) is classified Pathogenic/Likely pathogenic in PIGN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-11-17). AlphaMissense: likely pathogenic (0.9751); Very rare (popmax 0.00221%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PIGN p.Arg95Trp (c.283C>T)?

PIGN p.Arg95Trp (c.283C>T) is associated with Inborn genetic diseases, multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

How common is PIGN p.Arg95Trp (c.283C>T) in the general population?

PIGN p.Arg95Trp (c.283C>T) is very rare (popmax 0.00221%, nfe) (gnomAD).

What do computational predictors say about PIGN p.Arg95Trp (c.283C>T)?

AlphaMissense predicts likely pathogenic (score 0.9751) — an in-silico prediction, not a clinical call.

PIGN p.Arg95Trp

c.283C>T · rs558341655 · VCV378361

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9751 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9751	likely pathogenic ✓ concordant with ClinVar · top 4% in PIGN
REVEL	0.79	moderately pathogenic-leaning
SaProt	LLR -17.28	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.9	GERP 0.94, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,181 bp · p 0.39 · regional, not allelic
Overall
CADD	29.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 26/1,178,928 alleles

Filtering AF 0.00153% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0013%

Overall 0.00174% 28/1,612,356 alleles · very rare exomes 28/1,460,066 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00221%	45,343
African / African-American	0.00133%	75,026
South Asian	0.0011%	90,718

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.Arg95Trp
Coding: c.283C>T
MANE Select: NM_176787
dbSNP: rs558341655
Type: single nucleotide variant
Location: chr18:62157747 (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.Arg95Gln Pathogenic/Likely pathogenic ★★ same residue
PIGN p.Arg95= Likely benign ★ 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

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-arg95trp (accessed [today's date]).

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