Is YARS2 p.Ser8Phe (c.23C>T) pathogenic?

YARS2 p.Ser8Phe (c.23C>T) is classified Uncertain significance in YARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-22). AlphaMissense: likely benign (0.0771); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with YARS2 p.Ser8Phe (c.23C>T)?

YARS2 p.Ser8Phe (c.23C>T) is associated with Inborn genetic diseases (ClinVar).

How common is YARS2 p.Ser8Phe (c.23C>T) in the general population?

YARS2 p.Ser8Phe (c.23C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about YARS2 p.Ser8Phe (c.23C>T)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

YARS2 p.Ser8Phe

c.23C>T · VCV3983047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.098	moderately benign-leaning
SaProt	LLR -7.40	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 -2.3
Regional constraint	o/e 1.00	unconstrained · MANE · 8,667 bp · p 0.93 · regional, not allelic
Overall
CADD	4.522	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: YARS2
Protein: p.Ser8Phe
Coding: c.23C>T
MANE Select: NM_001040436
Type: single nucleotide variant
Location: chr12:32755852 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.57 · 2 PDB

Full YARS2 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

YARS2 p.Ala139Val Uncertain significance ★★ ⚠ same condition
YARS2 p.Ala31Thr Uncertain significance ★★ ⚠ same condition
YARS2 p.Ala31Val Uncertain significance ★★ ⚠ same condition
YARS2 p.Ala396Gly Uncertain significance ★★ same condition
YARS2 p.Ala94Thr Uncertain significance ★★ ⚠ same condition
YARS2 p.Arg118Leu Uncertain significance ★★ ⚠ same condition
YARS2 p.Arg136Cys Uncertain significance ★★ ⚠ same condition
YARS2 p.Gln36Arg 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/yars2-p-ser8phe (accessed [today's date]).

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