Is CBFA2T2 p.Ser314Arg (c.940A>C) pathogenic?

CBFA2T2 p.Ser314Arg (c.940A>C) is classified Uncertain significance in CBFA2T2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: ambiguous (0.4518); Ultra-rare (popmax 0.01%, amr).

How common is CBFA2T2 p.Ser314Arg (c.940A>C) in the general population?

CBFA2T2 p.Ser314Arg (c.940A>C) is ultra-rare (popmax 0.01%, amr) (gnomAD).

What do computational predictors say about CBFA2T2 p.Ser314Arg (c.940A>C)?

AlphaMissense predicts ambiguous (score 0.4518) — an in-silico prediction, not a clinical call.

CBFA2T2 p.Ser314Arg

c.940A>C · rs1000104269 · VCV3137936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4518 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.01%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4518	ambiguous
REVEL	0.047	moderately benign-leaning
SaProt	LLR -5.84	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 5.4, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 150 kb · p 1.3e-05 · regional, not allelic
Overall
CADD	20.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S323R vs ClinVar S314R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.01% Admixed American · 6/59,922 alleles

Filtering AF 0.00429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.000745% 12/1,610,576 alleles · ultra-rare exomes 3/1,458,436 · genomes 9/152,140 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.01%	9,987
African / African-American	0.00668%	14,974
Remaining individualsnot grpmax-eligible	0.0016%	62,348

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: CBFA2T2
Protein: p.Ser314Arg
Coding: c.940A>C
MANE Select: NM_001032999
dbSNP: rs1000104269
Type: single nucleotide variant
Location: chr20:33625011 (GRCh38)
Gene constraint: LOEUF 0.314 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.92

Full CBFA2T2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBFA2T2 c.35-32725G>A Uncertain significance ★ ⚠ same type
CBFA2T2 c.35-32739G>T Uncertain significance ★ ⚠ same type
CBFA2T2 c.35-32746G>A Uncertain significance ★ ⚠ same type
CBFA2T2 c.35-32749A>G Uncertain significance ★ ⚠ same type
CBFA2T2 c.35-32751C>T Uncertain significance ★ ⚠ same type
CBFA2T2 p.Ala184Thr Uncertain significance ★ ⚠ same type
CBFA2T2 p.Ala186Val Uncertain significance ★ ⚠ same type
CBFA2T2 p.Ala345Val 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/cbfa2t2-p-ser314arg (accessed [today's date]).

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