Is YTHDF2 p.Asn173Ser (c.518A>G) pathogenic?

YTHDF2 p.Asn173Ser (c.518A>G) is classified Likely benign in YTHDF2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). AlphaMissense: likely benign (0.0422); Rare (popmax 0.134%, eas).

How common is YTHDF2 p.Asn173Ser (c.518A>G) in the general population?

YTHDF2 p.Asn173Ser (c.518A>G) is rare (popmax 0.134%, eas) (gnomAD).

What do computational predictors say about YTHDF2 p.Asn173Ser (c.518A>G)?

AlphaMissense predicts likely benign (score 0.0422) — an in-silico prediction, not a clinical call.

YTHDF2 p.Asn173Ser

c.518A>G · VCV3333751

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0422 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0422	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -5.59	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 2.1	GERP 0.12, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 6,311 bp · p 3.2e-05 · regional, not allelic
Overall
CADD	7.539	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.134% East Asian · 60/44,882 alleles

Filtering AF 0.107% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0968%

Overall 0.00719% 116/1,614,186 alleles · rare exomes 111/1,461,894 · genomes 5/152,292 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.134%	748
Remaining individualsnot grpmax-eligible	0.008%	12,502
South Asian	0.00659%	15,181
African / African-American	0.004%	25,011
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Admixed American	0.00333%	30,006
European (non-Finnish)	0.0033%	30,257

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: YTHDF2
Protein: p.Asn173Ser
Coding: c.518A>G
MANE Select: NM_016258
Type: single nucleotide variant
Location: chr1:28742788 (GRCh38)
Gene constraint: LOEUF 0.132 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 61.14 · 29 PDB
Residue 173: 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.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
YTHDF2 p.Glu8Gln 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-asn173ser (accessed [today's date]).

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