Is PIGN p.Tyr511= (c.1533T>C) pathogenic?

PIGN p.Tyr511= (c.1533T>C) is classified Likely benign in PIGN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-23). Very rare (popmax 0.00399%, nfe); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 1.

What condition is associated with PIGN p.Tyr511= (c.1533T>C)?

PIGN p.Tyr511= (c.1533T>C) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

How common is PIGN p.Tyr511= (c.1533T>C) in the general population?

PIGN p.Tyr511= (c.1533T>C) is very rare (popmax 0.00399%, nfe) (gnomAD).

PIGN p.Tyr511=

c.1533T>C · rs2034805244 · VCV2915348

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00399%, nfe)

Conditions

multiple congenital anomalies-hypotonia-seizures syndrome 1

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 -0.023	GERP -3.2, phastCons 0.009
Overall
CADD	2.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00399% European (non-Finnish) · 47/1,179,350 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00304% 49/1,613,028 alleles · very rare exomes 48/1,460,838 · genomes 1/152,190 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00399%	25,093
Remaining individualsnot grpmax-eligible	0.0016%	62,412
South Asian	0.0011%	91,020

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.Tyr511=
Coding: c.1533T>C
MANE Select: NM_176787
dbSNP: rs2034805244
Type: single nucleotide variant
Location: chr18:62109875 (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

multiple congenital anomalies-hypotonia-seizures syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PIGN p.Tyr511Ter Pathogenic ★ 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-tyr511 (accessed [today's date]).

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