Is PSAT1 p.Val35Asp (c.104T>A) pathogenic?

PSAT1 p.Val35Asp (c.104T>A) is classified Uncertain significance in PSAT1 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-01-13). AlphaMissense: likely benign (0.2667); Ultra-rare (popmax 0.0156%, eas); Associated with PSAT deficiency.

What condition is associated with PSAT1 p.Val35Asp (c.104T>A)?

PSAT1 p.Val35Asp (c.104T>A) is associated with PSAT deficiency (ClinVar).

How common is PSAT1 p.Val35Asp (c.104T>A) in the general population?

PSAT1 p.Val35Asp (c.104T>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about PSAT1 p.Val35Asp (c.104T>A)?

AlphaMissense predicts likely benign (score 0.2667) — an in-silico prediction, not a clinical call.

PSAT1 p.Val35Asp

c.104T>A · rs761364177 · VCV912616

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2667 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PSAT deficiency

Computational evidence

Protein change
AlphaMissense	0.2667	likely benign
REVEL	0.228	benign-leaning
SaProt	LLR -8.15	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 1.9	phastCons 0.17
Regional constraint	o/e 0.89	unconstrained · MANE · 32 kb · p 0.02 · regional, not allelic
Overall
CADD	21.6	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 0.0156% East Asian · 7/44,832 alleles

Filtering AF 0.00727% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000435% 7/1,609,120 alleles · ultra-rare exomes 5/1,457,362 · genomes 2/151,758 · 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: PSAT1
Protein: p.Val35Asp
Coding: c.104T>A
MANE Select: NM_058179
dbSNP: rs761364177
Type: single nucleotide variant
Location: chr9:78300645 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.09 · 3 PDB
Residue 35: a β-strand

Full PSAT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PSAT deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PSAT1 p.Arg222Ter Pathogenic/Likely pathogenic ★★ same condition
PSAT1 p.Asp100Ala Pathogenic/Likely pathogenic ★★ same condition
PSAT1 p.Ala112Val Uncertain significance ★★ ⚠ same condition
PSAT1 p.Ala265Thr Uncertain significance ★★ ⚠ same condition
PSAT1 p.Arg222Gln Uncertain significance ★★ ⚠ same condition
PSAT1 p.Asn236His Uncertain significance ★★ ⚠ same condition
PSAT1 p.Asn302Ser Uncertain significance ★★ ⚠ same condition
PSAT1 p.Asp167Asn 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/psat1-p-val35asp (accessed [today's date]).

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