Is PSAP p.Val88Ala (c.263T>C) pathogenic?

PSAP p.Val88Ala (c.263T>C) is classified Uncertain significance in PSAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). AlphaMissense: likely benign (0.0779); Ultra-rare (popmax 0.0165%, mid).

How common is PSAP p.Val88Ala (c.263T>C) in the general population?

PSAP p.Val88Ala (c.263T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PSAP p.Val88Ala (c.263T>C)?

AlphaMissense predicts likely benign (score 0.0779) — an in-silico prediction, not a clinical call.

PSAP p.Val88Ala

c.263T>C · VCV4882541

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0779 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0779	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -4.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -3.8
Overall
CADD	4.206	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 0.0165% Middle Eastern · 1/6,058 alleles

Overall 0.000124% 2/1,614,068 alleles · ultra-rare exomes 2/1,461,762 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,058
European (non-Finnish)	8.47e-05%	1,179,967

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: PSAP
Protein: p.Val88Ala
Coding: c.263T>C
MANE Select: NM_002778
Type: single nucleotide variant
Location: chr10:71831238 (GRCh38)
Gene constraint: LOEUF 0.507 · pLI 0.95 (gnomAD)
Structure: AlphaFold pLDDT 73.90 · 21 PDB
Residue 88: the saposin b-type 1 domain; an α-helix

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

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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/psap-p-val88ala (accessed [today's date]).

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