Is PSPH p.Asp42Val (c.125A>T) pathogenic?

PSPH p.Asp42Val (c.125A>T) is classified Uncertain significance in PSPH (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely benign (0.1465); Very rare (popmax 0.00668%, eas); Associated with Inborn genetic diseases.

What condition is associated with PSPH p.Asp42Val (c.125A>T)?

PSPH p.Asp42Val (c.125A>T) is associated with Inborn genetic diseases (ClinVar).

How common is PSPH p.Asp42Val (c.125A>T) in the general population?

PSPH p.Asp42Val (c.125A>T) is very rare (popmax 0.00668%, eas) (gnomAD).

What do computational predictors say about PSPH p.Asp42Val (c.125A>T)?

AlphaMissense predicts likely benign (score 0.1465) — an in-silico prediction, not a clinical call.

PSPH p.Asp42Val

c.125A>T · rs779079384 · VCV2614084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1465 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1465	likely benign
REVEL	0.532	indeterminate
SaProt	LLR -9.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Pangolin	Δ0.20	gain · loss 0.17 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 4.6	GERP 4.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 9,447 bp · p 0.0022 · regional, not allelic
Overall
CADD	22.5	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 0.00668% East Asian · 3/44,900 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000248% 4/1,614,130 alleles · very rare exomes 3/1,461,886 · genomes 1/152,244 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,967
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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: PSPH
Protein: p.Asp42Val
Coding: c.125A>T
MANE Select: NM_004577
dbSNP: rs779079384
Type: single nucleotide variant
Location: chr7:56021088 (GRCh38)
Gene constraint: LOEUF 1.063 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 92.88 · 6 PDB
Residue 42: a turn

Full PSPH 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

PSPH p.Asp42= Benign/Likely benign ★★ same residue
PSPH p.Asn124Ser Uncertain significance ★★ ⚠ same condition
PSPH p.Glu117Asp Uncertain significance ★★ ⚠ same condition
PSPH p.Glu225Lys Uncertain significance ★★ ⚠ same condition
PSPH p.Tyr212Cys Uncertain significance ★★ ⚠ same condition
PSPH p.Ala192Thr Uncertain significance ★ ⚠ same condition
PSPH p.Ala192Val Conflicting classifications of pathogenicity ★ ⚠ same condition
PSPH p.Ala209Thr 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/psph-p-asp42val (accessed [today's date]).

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