Is YTHDC1 p.Asp56Tyr (c.166G>T) pathogenic?

YTHDC1 p.Asp56Tyr (c.166G>T) is classified Uncertain significance in YTHDC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: ambiguous (0.3595); Very rare (popmax 0.00161%, nfe).

How common is YTHDC1 p.Asp56Tyr (c.166G>T) in the general population?

YTHDC1 p.Asp56Tyr (c.166G>T) is very rare (popmax 0.00161%, nfe) (gnomAD).

What do computational predictors say about YTHDC1 p.Asp56Tyr (c.166G>T)?

AlphaMissense predicts ambiguous (score 0.3595) — an in-silico prediction, not a clinical call.

YTHDC1 p.Asp56Tyr

c.166G>T · rs1021974425 · VCV3191636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3595 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00161%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3595	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -7.83	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.7	phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 4,938 bp · p 0.3 · regional, not allelic
Overall
CADD	25.0	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 0.00161% European (non-Finnish) · 19/1,179,900 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00083%

Overall 0.00124% 20/1,612,644 alleles · very rare exomes 16/1,461,288 · genomes 4/151,356 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00161%	62,100
African / African-American	0.00134%	74,628

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: YTHDC1
Protein: p.Asp56Tyr
Coding: c.166G>T
MANE Select: NM_001031732
dbSNP: rs1021974425
Type: single nucleotide variant
Location: chr4:68337865 (GRCh38)
Gene constraint: LOEUF 0.184 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 60.41 · 109 PDB
Residue 56: the 'disordered' region

Full YTHDC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

YTHDC1 p.Arg113Gln Uncertain significance ★ ⚠ same type
YTHDC1 p.Arg136Gln Uncertain significance ★ ⚠ same type
YTHDC1 p.Arg301Ser Uncertain significance ★ ⚠ same type
YTHDC1 p.Arg341Gln Uncertain significance ★ ⚠ same type
YTHDC1 p.Arg522His Uncertain significance ★ ⚠ same type
YTHDC1 p.Arg526Gly Uncertain significance ★ ⚠ same type
YTHDC1 p.Arg535Cys Uncertain significance ★ ⚠ same type
YTHDC1 p.Arg560Gly 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/ythdc1-p-asp56tyr (accessed [today's date]).

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