Is BBOF1 p.Lys68Asn (c.204G>T) pathogenic?

BBOF1 p.Lys68Asn (c.204G>T) is classified Uncertain significance in BBOF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: ambiguous (0.4517); Rare (popmax 0.11%, nfe).

How common is BBOF1 p.Lys68Asn (c.204G>T) in the general population?

BBOF1 p.Lys68Asn (c.204G>T) is rare (popmax 0.11%, nfe) (gnomAD).

What do computational predictors say about BBOF1 p.Lys68Asn (c.204G>T)?

AlphaMissense predicts ambiguous (score 0.4517) — an in-silico prediction, not a clinical call.

BBOF1 p.Lys68Asn

c.204G>T · rs61752569 · VCV2346657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4517 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.11%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4517	ambiguous
REVEL	0.033	moderately benign-leaning
SaProt	LLR -7.95	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 45 kb · p 0.007 · regional, not allelic
Overall
CADD	21.1	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 0.11% European (non-Finnish) · 1,293/1,176,796 alleles

Filtering AF 0.105% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.103%

Overall 0.082% 1,318/1,607,558 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.11%	910
Remaining individualsnot grpmax-eligible	0.0257%	3,895
African / African-American	0.00934%	10,707
Finnishnot grpmax-eligible	0.00314%	31,887

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: BBOF1
Protein: p.Lys68Asn
Coding: c.204G>T
MANE Select: NM_025057
dbSNP: rs61752569
Type: single nucleotide variant
Location: chr14:74023063 (GRCh38)
Gene constraint: LOEUF 1.032 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.40

Full BBOF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ALDH6A1 c.112-11G>T Benign ★★ same type
ALDH6A1 c.731-12T>C Benign/Likely benign ★★ same type
ALDH6A1 c.*494A>T Benign ★★ same type
ALDH6A1 p.Asp137Ala Uncertain significance ★ same type
ALDH6A1 p.Met198Leu Uncertain significance ★ ⚠ same type
ALDH6A1 p.Thr96Ile Uncertain significance ★ ⚠ same type
ALDH6A1 p.Val49Ile Conflicting classifications of pathogenicity ★ ⚠ same type
BBOF1 p.Ala317Thr 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/bbof1-p-lys68asn (accessed [today's date]).

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