Is YTHDF3 p.Ala264Gly (c.791C>G) pathogenic?

YTHDF3 p.Ala264Gly (c.791C>G) is classified Likely benign in YTHDF3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-06). AlphaMissense: likely benign (0.1096); Absent from gnomAD v4.1; Associated with complex neurodevelopmental disorder.

What condition is associated with YTHDF3 p.Ala264Gly (c.791C>G)?

YTHDF3 p.Ala264Gly (c.791C>G) is associated with complex neurodevelopmental disorder (ClinVar).

How common is YTHDF3 p.Ala264Gly (c.791C>G) in the general population?

YTHDF3 p.Ala264Gly (c.791C>G) is absent from gnomAD v4.1 (gnomAD).

How is Non-specific syndromic intellectual disability inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about YTHDF3 p.Ala264Gly (c.791C>G)?

AlphaMissense predicts likely benign (score 0.1096) — an in-silico prediction, not a clinical call.

YTHDF3 p.Ala264Gly

c.791C>G · VCV4851325

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1096 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt

Conditions

complex neurodevelopmental disorder

Computational evidence

Protein change
AlphaMissense	0.1096	likely benign
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense and SaProt both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.9, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 501 bp · p 0.91 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; SaProt is an independent agreement signal.

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: YTHDF3
Protein: p.Ala264Gly
Coding: c.791C>G
MANE Select: NM_152758
Type: single nucleotide variant
Location: chr8:63186802 (GRCh38)
Gene constraint: LOEUF 0.272 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 61.63 · 3 PDB
Residue 264: the 'disordered' region

Full YTHDF3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

complex neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Non-specific syndromic intellectual disability (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Childhood, Infancy

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/ythdf3-p-ala264gly (accessed [today's date]).

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