Is YEATS2 p.Ile1226Val (c.3676A>G) pathogenic?

YEATS2 p.Ile1226Val (c.3676A>G) is classified Uncertain significance in YEATS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-14). AlphaMissense: likely benign (0.0624); Very rare (popmax 0.00134%, afr).

How common is YEATS2 p.Ile1226Val (c.3676A>G) in the general population?

YEATS2 p.Ile1226Val (c.3676A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about YEATS2 p.Ile1226Val (c.3676A>G)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

YEATS2 p.Ile1226Val

c.3676A>G · rs748616345 · VCV2623943

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.37	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 4.7	GERP -0.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 95 kb · p 1.4e-05 · regional, not allelic
Overall
CADD	12.08	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 0.00134% African / African-American · 1/74,906 alleles

Overall 0.000124% 2/1,614,048 alleles · very rare exomes 1/1,461,894 · genomes 1/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,906
South Asian	0.0011%	91,088

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.Ile1226Val
Coding: c.3676A>G
MANE Select: NM_018023
dbSNP: rs748616345
Type: single nucleotide variant
Location: chr3:183804080 (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-ile1226val (accessed [today's date]).

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