Is MACF1 p.Ala5867= (c.17601C>T) pathogenic?

MACF1 p.Ala5867= (c.17601C>T) is classified Likely benign in MACF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). Rare (popmax 0.479%, sas).

How common is MACF1 p.Ala5867= (c.17601C>T) in the general population?

MACF1 p.Ala5867= (c.17601C>T) is rare (popmax 0.479%, sas) (gnomAD).

MACF1 p.Ala5867=

c.17601C>T · VCV4967717

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.479%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.065	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.087	GERP -1.8, phastCons 0.001
Overall
CADD	6.945	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.479% South Asian · 436/91,000 alleles

Filtering AF 0.442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.427%

Overall 0.0289% 466/1,611,010 alleles · rare exomes 441/1,460,656 · genomes 25/150,354 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.479%	209
Remaining individualsnot grpmax-eligible	0.0449%	2,229
European (non-Finnish)	0.00017%	589,494

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.Ala5867=
Coding: c.17601C>T
MANE Select: NM_001394062
Type: single nucleotide variant
Location: chr1:39434449 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)

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

Similar variants

MACF1 p.Ala5867Thr Uncertain significance ★ ⚠ same residue
MACF1 p.Arg7251Pro Likely pathogenic ★★ same type
MACF1 p.Ala5598Ser Uncertain significance ★★ same type
MACF1 p.Ala601Pro Uncertain significance ★★ ⚠ same type
MACF1 p.Arg1196Gln Uncertain significance ★★ ⚠ same type
MACF1 p.Arg30Gln Uncertain significance ★★ same type
MACF1 p.Arg3713Cys Uncertain significance ★★ ⚠ same type
MACF1 p.Arg4674Cys 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/macf1-p-ala5867 (accessed [today's date]).

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