Is PPCS p.Ala237Thr (c.709G>A) pathogenic?

PPCS p.Ala237Thr (c.709G>A) is classified Uncertain significance in PPCS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-09). AlphaMissense: likely benign (0.0653); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with PPCS p.Ala237Thr (c.709G>A)?

PPCS p.Ala237Thr (c.709G>A) is associated with Inborn genetic diseases (ClinVar).

How common is PPCS p.Ala237Thr (c.709G>A) in the general population?

PPCS p.Ala237Thr (c.709G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PPCS p.Ala237Thr (c.709G>A)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

PPCS p.Ala237Thr

c.709G>A · rs1482478128 · VCV1481787

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.86	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 0.14	GERP -0.096, phastCons 0.004
Regional constraint	o/e 0.69	unconstrained · MANE · 2,669 bp · p 5.9e-05 · regional, not allelic
Overall
CADD	7.381	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 0.00333% Admixed American · 2/60,000 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000743% 12/1,613,994 alleles · very rare exomes 7/1,461,840 · genomes 5/152,154 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,000
African / African-American	0.00267%	37,448
European (non-Finnish)	0.000678%	147,505

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.Ala237Thr
Coding: c.709G>A
MANE Select: NM_024664
dbSNP: rs1482478128
Type: single nucleotide variant
Location: chr1:42459699 (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-ala237thr (accessed [today's date]).

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