Is PIGN p.Val620= (c.1860G>A) pathogenic?

PIGN p.Val620= (c.1860G>A) is classified Conflicting classifications of pathogenicity in PIGN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-11-23). Rare (popmax 0.185%, afr); Associated with multiple congenital anomalies-hypotonia-seizures syndrome 1.

What condition is associated with PIGN p.Val620= (c.1860G>A)?

PIGN p.Val620= (c.1860G>A) is associated with multiple congenital anomalies-hypotonia-seizures syndrome 1 (ClinVar).

How common is PIGN p.Val620= (c.1860G>A) in the general population?

PIGN p.Val620= (c.1860G>A) is rare (popmax 0.185%, afr) (gnomAD).

PIGN p.Val620=

c.1860G>A · rs374172871 · VCV588838

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.185%, afr)

Conditions

multiple congenital anomalies-hypotonia-seizures syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	acceptor loss · deltas
Pangolin	Δ0.31	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.41	GERP -0.4, phastCons 0.15
Overall
CADD	8.157	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.185% African / African-American · 133/71,706 alleles

Filtering AF 0.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.15%

Overall 0.00949% 145/1,528,126 alleles · rare exomes 55/1,375,914 · genomes 90/152,212 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.185%	539
Remaining individualsnot grpmax-eligible	0.0118%	8,479
Admixed American	0.00426%	23,478
European (non-Finnish)	0.000265%	377,666

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.Val620=
Coding: c.1860G>A
MANE Select: NM_176787
dbSNP: rs374172871
Type: single nucleotide variant
Location: chr18:62102902 (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.Val620Leu 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-val620 (accessed [today's date]).

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