Is SBF1 p.Arg656Gln (c.1967G>A) pathogenic?

SBF1 p.Arg656Gln (c.1967G>A) is classified Uncertain significance in SBF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-02). AlphaMissense: likely pathogenic (0.8797); Very rare (popmax 0.00401%, afr).

How common is SBF1 p.Arg656Gln (c.1967G>A) in the general population?

SBF1 p.Arg656Gln (c.1967G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about SBF1 p.Arg656Gln (c.1967G>A)?

AlphaMissense predicts likely pathogenic (score 0.8797) — an in-silico prediction, not a clinical call.

SBF1 p.Arg656Gln

c.1967G>A · rs778794053 · VCV1375341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8797 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8797	likely pathogenic
REVEL	0.345	indeterminate
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.67 · regional, not allelic
Overall
CADD	24.1	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 R657Q vs ClinVar R656Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,904 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000682% 11/1,612,962 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,968
East Asian	0.00223%	44,880
Admixed American	0.00167%	59,968
European (non-Finnish)	0.000509%	196,655

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: SBF1
Protein: p.Arg656Gln
Coding: c.1967G>A
MANE Select: NM_002972
dbSNP: rs778794053
Type: single nucleotide variant
Location: chr22:50462871 (GRCh38)
Gene constraint: LOEUF 0.381 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 74.72

Full SBF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SBF1 p.Arg656Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
SBF1 p.Arg656= Likely benign ★ same residue
SBF1 c.3826+1G>A Pathogenic/Likely pathogenic ★★ same type
SBF1 p.Met417Val Pathogenic/Likely pathogenic ★★ ⚠ same type
SBF1 c.1431+6A>T Uncertain significance ★★ same type
SBF1 c.1636+4C>T Uncertain significance ★★ same type
SBF1 c.1899+3G>A Uncertain significance ★★ same type
SBF1 c.2643+6C>T 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/sbf1-p-arg656gln (accessed [today's date]).

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