Is YTHDF1 p.Asn71Ser (c.212A>G) pathogenic?

YTHDF1 p.Asn71Ser (c.212A>G) is classified Likely benign in YTHDF1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-12-07). AlphaMissense: likely benign (0.0479); Ultra-rare (popmax 0.0878%, sas).

How common is YTHDF1 p.Asn71Ser (c.212A>G) in the general population?

YTHDF1 p.Asn71Ser (c.212A>G) is ultra-rare (popmax 0.0878%, sas) (gnomAD).

What do computational predictors say about YTHDF1 p.Asn71Ser (c.212A>G)?

AlphaMissense predicts likely benign (score 0.0479) — an in-silico prediction, not a clinical call.

YTHDF1 p.Asn71Ser

c.212A>G · rs768838026 · VCV3191662

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0479 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0878%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0479	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -5.58	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 -0.53	GERP -4.3
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.25 · regional, not allelic
Overall
CADD	6.374	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 0.0878% South Asian · 80/91,076 alleles

Filtering AF 0.0722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0666%

Overall 0.00973% 157/1,614,054 alleles · ultra-rare exomes 146/1,461,856 · genomes 11/152,198 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0878%	1,138
Middle Eastern	0.0165%	6,062
East Asian	0.0156%	6,412
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.00517%	19,344
African / African-American	0.00267%	37,496
Admixed American	0.00167%	60,006

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.Asn71Ser
Coding: c.212A>G
MANE Select: NM_017798
dbSNP: rs768838026
Type: single nucleotide variant
Location: chr20:63203728 (GRCh38)
Gene constraint: LOEUF 0.515 · pLI 0.96 (gnomAD)
Structure: AlphaFold pLDDT 62.83 · 10 PDB

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.Ser252= Benign ★★ same type
YTHDF1 p.Val195= Benign ★★ same type
YTHDF1 p.Ala146Thr Uncertain significance ★ ⚠ same type
YTHDF1 p.Ala199Ser 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-asn71ser (accessed [today's date]).

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