Is MACF1 p.Lys5797= (c.17391A>G) pathogenic?

MACF1 p.Lys5797= (c.17391A>G) is classified Likely benign in MACF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). Very rare (popmax 0.00576%, nfe); Associated with Inborn genetic diseases.

What condition is associated with MACF1 p.Lys5797= (c.17391A>G)?

MACF1 p.Lys5797= (c.17391A>G) is associated with Inborn genetic diseases (ClinVar).

How common is MACF1 p.Lys5797= (c.17391A>G) in the general population?

MACF1 p.Lys5797= (c.17391A>G) is very rare (popmax 0.00576%, nfe) (gnomAD).

MACF1 p.Lys5797=

c.17391A>G · rs762712850 · VCV3121852

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00576%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.152	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.61	GERP -3, phastCons 0.61
Overall
CADD	4.374	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00576% European (non-Finnish) · 68/1,179,998 alleles

Filtering AF 0.00462% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00422%

Overall 0.00465% 75/1,613,984 alleles · very rare exomes 68/1,461,796 · genomes 7/152,188 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00576%	17,353
African / African-American	0.004%	24,973
South Asian	0.0022%	45,543
Admixed American	0.00167%	59,986
Remaining individualsnot grpmax-eligible	0.0016%	62,486

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: MACF1
Protein: p.Lys5797=
Coding: c.17391A>G
MANE Select: NM_001394062
dbSNP: rs762712850
Type: single nucleotide variant
Location: chr1:39432588 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)

Full MACF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MACF1 p.Ala5598Ser Uncertain significance ★★ same condition
MACF1 p.Ala601Pro Uncertain significance ★★ ⚠ same condition
MACF1 p.Arg30Gln Uncertain significance ★★ same condition
MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same condition
MACF1 p.Arg4674Cys Uncertain significance ★★ same condition
MACF1 p.Arg5490Gln Uncertain significance ★★ ⚠ same condition
MACF1 p.Arg5875Cys Uncertain significance ★★ same condition
MACF1 p.Arg6864Gln Uncertain significance ★★ 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/macf1-p-lys5797 (accessed [today's date]).

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