Is YEATS2 p.Pro613Ser (c.1837C>T) pathogenic?

YEATS2 p.Pro613Ser (c.1837C>T) is classified Uncertain significance in YEATS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-04). AlphaMissense: likely benign (0.1036); Very rare (popmax 0.00333%, amr).

How common is YEATS2 p.Pro613Ser (c.1837C>T) in the general population?

YEATS2 p.Pro613Ser (c.1837C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about YEATS2 p.Pro613Ser (c.1837C>T)?

AlphaMissense predicts likely benign (score 0.1036) — an in-silico prediction, not a clinical call.

YEATS2 p.Pro613Ser

c.1837C>T · VCV4606071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1036 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1036	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 95 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,026 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,166 alleles · very rare exomes 2/1,461,882 · genomes 0/152,284 · joint denominator

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: YEATS2
Protein: p.Pro613Ser
Coding: c.1837C>T
MANE Select: NM_018023
Type: single nucleotide variant
Location: chr3:183762169 (GRCh38)
Gene constraint: LOEUF 0.552 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.50 · 5 PDB

Full YEATS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

YEATS2 p.Asp12Asn Uncertain significance ★★ ⚠ same type
YEATS2 p.His1216Arg Uncertain significance ★★ ⚠ same type
YEATS2 c.292-27T>C Benign/Likely benign ★★ same type
YEATS2 c.3582+10A>G Benign ★★ same type
YEATS2 p.Ala1000Thr Benign/Likely benign ★★ same type
YEATS2 p.Ala603Thr Likely benign ★★ same type
YEATS2 p.Ile495Met Likely benign ★★ same type
YEATS2 p.Thr534Lys Benign/Likely benign ★★ 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/yeats2-p-pro613ser (accessed [today's date]).

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