Is YTHDF2 p.Ser201Gly (c.601A>G) pathogenic?

YTHDF2 p.Ser201Gly (c.601A>G) is classified Uncertain significance in YTHDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0544); Absent from gnomAD v4.1.

How common is YTHDF2 p.Ser201Gly (c.601A>G) in the general population?

YTHDF2 p.Ser201Gly (c.601A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about YTHDF2 p.Ser201Gly (c.601A>G)?

AlphaMissense predicts likely benign (score 0.0544) — an in-silico prediction, not a clinical call.

YTHDF2 p.Ser201Gly

c.601A>G · VCV4203360

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0544 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0544	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 6,311 bp · p 3.2e-05 · regional, not allelic
Overall
CADD	20.4	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: YTHDF2
Protein: p.Ser201Gly
Coding: c.601A>G
MANE Select: NM_016258
Type: single nucleotide variant
Location: chr1:28742871 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.14 · 29 PDB
Residue 201: the 'localization to mrna processing bodies (p-bodies)' region

Full YTHDF2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

YTHDF2 p.Ser201Asn Uncertain significance ★ ⚠ same residue
YTHDF2 p.Ala170Gly Uncertain significance ★ ⚠ same type
YTHDF2 p.Ala285Gly Uncertain significance ★ ⚠ same type
YTHDF2 p.Arg10Lys Uncertain significance ★ ⚠ same type
YTHDF2 p.Arg393Trp Uncertain significance ★ ⚠ same type
YTHDF2 p.Arg574His Uncertain significance ★ ⚠ same type
YTHDF2 p.Asp496Asn Uncertain significance ★ ⚠ same type
YTHDF2 p.Gln327Arg Uncertain significance ★ ⚠ same type

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/ythdf2-p-ser201gly (accessed [today's date]).

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