Is PIGP p.Phe20Ser (c.59T>C) pathogenic?

PIGP p.Phe20Ser (c.59T>C) is classified Uncertain significance in PIGP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-10). AlphaMissense: likely pathogenic (0.795); Very rare (popmax 0.00475%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PIGP p.Phe20Ser (c.59T>C)?

PIGP p.Phe20Ser (c.59T>C) is associated with Inborn genetic diseases (ClinVar).

How common is PIGP p.Phe20Ser (c.59T>C) in the general population?

PIGP p.Phe20Ser (c.59T>C) is very rare (popmax 0.00475%, nfe) (gnomAD).

What do computational predictors say about PIGP p.Phe20Ser (c.59T>C)?

AlphaMissense predicts likely pathogenic (score 0.795) — an in-silico prediction, not a clinical call.

PIGP p.Phe20Ser

c.59T>C · rs771037472 · VCV1373317

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.795 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00475%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.795	likely pathogenic
REVEL	0.203	benign-leaning
SaProt	LLR -11.47	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP -0.86, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 6,930 bp · p 0.66 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F44S vs ClinVar F20S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00475% European (non-Finnish) · 56/1,180,030 alleles

Filtering AF 0.00375% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00337%

Overall 0.00359% 58/1,614,130 alleles · very rare exomes 56/1,461,876 · genomes 2/152,254 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00475%	21,072
Remaining individualsnot grpmax-eligible	0.0016%	62,484
African / African-American	0.00133%	74,958

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: PIGP
Protein: p.Phe20Ser
Coding: c.59T>C
MANE Select: NM_153682
dbSNP: rs771037472
Type: single nucleotide variant
Location: chr21:37072457 (GRCh38)
Gene constraint: LOEUF 1.937 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.42

Full PIGP 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

PIGP c.-12G>A Uncertain significance ★★ ⚠ same condition
PIGP c.-8C>T Uncertain significance ★★ ⚠ same condition
PIGP p.Ala95Glu Uncertain significance ★★ ⚠ same condition
PIGP p.Ile108Phe Uncertain significance ★★ ⚠ same condition
PIGP p.Ile28Arg Uncertain significance ★★ ⚠ same condition
PIGP p.Ile76Phe Uncertain significance ★★ ⚠ same condition
PIGP p.Leu111Phe Uncertain significance ★★ same condition
PIGP p.Leu72Phe 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/pigp-p-phe20ser (accessed [today's date]).

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