Is PPT1 p.Asp237Val (c.710A>T) pathogenic?

PPT1 p.Asp237Val (c.710A>T) is classified Uncertain significance in PPT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.2017); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with PPT1 p.Asp237Val (c.710A>T)?

PPT1 p.Asp237Val (c.710A>T) is associated with Inborn genetic diseases (ClinVar).

How common is PPT1 p.Asp237Val (c.710A>T) in the general population?

PPT1 p.Asp237Val (c.710A>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about PPT1 p.Asp237Val (c.710A>T)?

AlphaMissense predicts likely benign (score 0.2017) — an in-silico prediction, not a clinical call.

PPT1 p.Asp237Val

c.710A>T · VCV4143440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2017 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2017	likely benign
REVEL	0.669	pathogenic-leaning
SaProt	LLR -1.95	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 23 kb · p 0.052 · regional, not allelic
Overall
CADD	23.7	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 0.0022% South Asian · 2/91,086 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000136%

Overall 0.000124% 2/1,613,852 alleles · very rare exomes 2/1,461,568 · genomes 0/152,284 · joint denominator

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: PPT1
Protein: p.Asp237Val
Coding: c.710A>T
MANE Select: NM_000310
Type: single nucleotide variant
Location: chr1:40078576 (GRCh38)
Gene constraint: LOEUF 0.733 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.05 · 1 PDB
Residue 237: a β-strand

Full PPT1 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

PPT1 p.Asp237= Likely benign ★ same residue
PPT1 p.Arg122Trp Pathogenic ★★ same condition
PPT1 p.Glu184Lys Pathogenic/Likely pathogenic ★★ same condition
PPT1 p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
PPT1 p.Thr75Pro Pathogenic ★★ same condition
PPT1 p.Ala171Val Uncertain significance ★★ ⚠ same condition
PPT1 p.Ala277Val Uncertain significance ★★ ⚠ same condition
PPT1 p.Arg164Gln 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/ppt1-p-asp237val (accessed [today's date]).

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