Is YTHDF1 p.Ser252= (c.756C>T) pathogenic?

YTHDF1 p.Ser252= (c.756C>T) is classified Benign in YTHDF1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). Common (popmax 5.84%, afr) — too common for a highly-penetrant pathogenic allele.

YTHDF1 p.Ser252=

Q: How common is YTHDF1 p.Ser252= (c.756C>T) in the general population?

YTHDF1 p.Ser252= (c.756C>T) is common (popmax 5.84%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.756C>T · rs79046601 · VCV786369

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.84%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.2	GERP -4.3
Overall
CADD	0.016	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.84% African / African-American · 4,383/75,036 alleles

Filtering AF 5.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.64%

Overall 0.309% 4,985/1,613,854 alleles · common exomes 2,458/1,461,568 · genomes 2,527/152,286 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.84%	17
Admixed American	0.408%	245
Remaining individualsnot grpmax-eligible	0.395%	253
Middle Eastern	0.198%	505
South Asian	0.0132%	7,590
European (non-Finnish)	0.00703%	14,217
East Asian	0.00668%	14,959

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: YTHDF1
Protein: p.Ser252=
Coding: c.756C>T
MANE Select: NM_017798
dbSNP: rs79046601
Type: single nucleotide variant
Location: chr20:63203184 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 62.83 · 10 PDB
Residue 252: the 'disordered' region

Full YTHDF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

YTHDF1 p.Asn497= Benign ★★ same type
YTHDF1 p.His375Tyr Benign ★★ same type
YTHDF1 p.Lys473= Benign ★★ same type
YTHDF1 p.Ser145= Benign ★★ same type
YTHDF1 p.Val195= Benign ★★ same type
YTHDF1 p.Ala146Thr Uncertain significance ★ ⚠ same type
YTHDF1 p.Ala199Ser Uncertain significance ★ ⚠ same type
YTHDF1 p.Ala302Gly 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/ythdf1-p-ser252 (accessed [today's date]).

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