Is PIGH p.Ser103Pro (c.307T>C) pathogenic?

PIGH p.Ser103Pro (c.307T>C) is classified Pathogenic/Likely pathogenic in PIGH (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-04-27). AlphaMissense: likely pathogenic (0.8977); Very rare (popmax 0.00449%, nfe); Associated with PIGH-related disorder.

What condition is associated with PIGH p.Ser103Pro (c.307T>C)?

PIGH p.Ser103Pro (c.307T>C) is associated with PIGH-related disorder, glycosylphosphatidylinositol biosynthesis defect 17 (ClinVar).

How common is PIGH p.Ser103Pro (c.307T>C) in the general population?

PIGH p.Ser103Pro (c.307T>C) is very rare (popmax 0.00449%, nfe) (gnomAD).

What do computational predictors say about PIGH p.Ser103Pro (c.307T>C)?

AlphaMissense predicts likely pathogenic (score 0.8977) — an in-silico prediction, not a clinical call.

PIGH p.Ser103Pro

c.307T>C · rs776038451 · VCV545631

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8977 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00449%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PIGH-related disorder

Computational evidence

Protein change
AlphaMissense	0.8977	likely pathogenic ✓ concordant with ClinVar
REVEL	0.25	benign-leaning
SaProt	LLR -11.92	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.3	GERP 2.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 10 kb · p 0.0035 · regional, not allelic
Overall
CADD	25.9	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 0.00449% European (non-Finnish) · 53/1,179,502 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00341% 55/1,613,474 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00449%	22,255
Remaining individualsnot grpmax-eligible	0.0016%	62,468
South Asian	0.0011%	91,072

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: PIGH
Protein: p.Ser103Pro
Coding: c.307T>C
MANE Select: NM_020806 · reported on NM_004569
dbSNP: rs776038451
Type: single nucleotide variant
Location: chr14:67593826 (GRCh38)

Full PIGH gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PIGH-related disorder

Also linked: glycosylphosphatidylinositol biosynthesis defect 17

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/pigh-p-ser103pro (accessed [today's date]).

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