Is BCS1L p.Pro344= (c.1032G>A) pathogenic?

BCS1L p.Pro344= (c.1032G>A) is classified Conflicting classifications of pathogenicity in BCS1L (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-22). Ultra-rare (popmax 0.0133%, amr); Associated with mitochondrial complex III deficiency nuclear type 1.

How common is BCS1L p.Pro344= (c.1032G>A) in the general population?

BCS1L p.Pro344= (c.1032G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

BCS1L p.Pro344=

Q: What condition is associated with BCS1L p.Pro344= (c.1032G>A)?

BCS1L p.Pro344= (c.1032G>A) is associated with mitochondrial complex III deficiency nuclear type 1, Bjornstad syndrome, GRACILE syndrome (ClinVar).

c.1032G>A · VCV3585657

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

mitochondrial complex III deficiency nuclear type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.091	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -13	GERP -4.6
Overall
CADD	0.439	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,994 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00279% 45/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,499
Remaining individualsnot grpmax-eligible	0.0064%	15,621
European (non-Finnish)	0.00254%	39,334
South Asian	0.0022%	45,542
African / African-American	0.00133%	74,922

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: BCS1L
Protein: p.Pro344=
Coding: c.1032G>A
MANE Select: NM_001079866
Type: single nucleotide variant
Location: chr2:218663158 (GRCh38)
Gene constraint: LOEUF 0.958 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.10

Full BCS1L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex III deficiency nuclear type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Bjornstad syndrome GRACILE syndrome

Similar variants

BCS1L p.Pro344Leu Uncertain significance ★★ ⚠ same residue
BCS1L p.Pro344Thr Uncertain significance ★ ⚠ same residue
BCS1L c.320+1G>T Pathogenic/Likely pathogenic ★★ same condition
BCS1L c.321-2A>G Likely pathogenic ★★ same condition
BCS1L c.889+1G>T Pathogenic/Likely pathogenic ★★ same condition
BCS1L c.889+2T>G Likely pathogenic ★★ same condition
BCS1L c.-50+388C>G Likely pathogenic ★★ same condition
BCS1L c.-50+405A>G Pathogenic/Likely pathogenic ★★ same condition

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/bcs1l-p-pro344 (accessed [today's date]).

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