Is PIGN p.Ser806Phe (c.2417C>T) pathogenic?

PIGN p.Ser806Phe (c.2417C>T) is classified Uncertain significance in PIGN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: likely pathogenic (0.9775); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PIGN p.Ser806Phe (c.2417C>T)?

PIGN p.Ser806Phe (c.2417C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PIGN p.Ser806Phe (c.2417C>T) in the general population?

PIGN p.Ser806Phe (c.2417C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PIGN p.Ser806Phe (c.2417C>T)?

AlphaMissense predicts likely pathogenic (score 0.9775) — an in-silico prediction, not a clinical call.

PIGN p.Ser806Phe

c.2417C>T · rs2512443851 · VCV2333782

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9775 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9775	likely pathogenic · top 4% in PIGN
REVEL	0.7	pathogenic-leaning
SaProt	LLR -13.48	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.38	donor loss · deltas
Pangolin	Δ0.29	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 109 kb · p 0.83 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PIGN
Protein: p.Ser806Phe
Coding: c.2417C>T
MANE Select: NM_176787
dbSNP: rs2512443851
Type: single nucleotide variant
Location: chr18:62085218 (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

Similar variants

PIGN c.1675-1G>T Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Arg613Ter Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Arg785His Likely pathogenic ★★ same condition
PIGN p.Arg95Trp Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Leu311Trp Pathogenic/Likely pathogenic ★★ same condition
PIGN p.Ala100Thr Uncertain significance ★★ ⚠ same condition
PIGN p.Ala805Thr Uncertain significance ★★ ⚠ same condition
PIGN p.Ala829Thr Uncertain significance ★★ ⚠ 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-ser806phe (accessed [today's date]).

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