Is PPCS p.Ser103Cys (c.308C>G) pathogenic?

PPCS p.Ser103Cys (c.308C>G) is classified Uncertain significance in PPCS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-12). AlphaMissense: likely benign (0.1124); Ultra-rare (popmax 0.0468%, eas); Associated with Inborn genetic diseases.

What condition is associated with PPCS p.Ser103Cys (c.308C>G)?

PPCS p.Ser103Cys (c.308C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PPCS p.Ser103Cys (c.308C>G) in the general population?

PPCS p.Ser103Cys (c.308C>G) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

What do computational predictors say about PPCS p.Ser103Cys (c.308C>G)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

PPCS p.Ser103Cys

c.308C>G · rs541879970 · VCV1447868

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -9.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP 2.1, phastCons 0.55
Regional constraint	o/e 1.04	unconstrained · MANE · 687 bp · p 0.55 · regional, not allelic
Overall
CADD	23.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0468% East Asian · 21/44,886 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.00514% 83/1,613,376 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0468%	2,137
Remaining individualsnot grpmax-eligible	0.0096%	10,417
African / African-American	0.00533%	18,773
European (non-Finnish)	0.00432%	23,138
South Asian	0.0011%	91,088

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: PPCS
Protein: p.Ser103Cys
Coding: c.308C>G
MANE Select: NM_001395517 · reported on NM_024664
dbSNP: rs541879970
Type: single nucleotide variant
Location: chr1:42456873 (GRCh38)

Full PPCS 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

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/ppcs-p-ser103cys (accessed [today's date]).

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