Is MACF1 p.Arg15Trp (c.43C>T) pathogenic?

MACF1 p.Arg15Trp (c.43C>T) is classified Likely benign in MACF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-26). AlphaMissense: ambiguous (0.3409); Ultra-rare (popmax 0.0107%, afr); Associated with Inborn genetic diseases.

What condition is associated with MACF1 p.Arg15Trp (c.43C>T)?

MACF1 p.Arg15Trp (c.43C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MACF1 p.Arg15Trp (c.43C>T) in the general population?

MACF1 p.Arg15Trp (c.43C>T) is ultra-rare (popmax 0.0107%, afr) (gnomAD).

What do computational predictors say about MACF1 p.Arg15Trp (c.43C>T)?

AlphaMissense predicts ambiguous (score 0.3409) — an in-silico prediction, not a clinical call.

MACF1 p.Arg15Trp

c.43C>T · VCV3869418

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3409 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3409	ambiguous
REVEL	0.27	benign-leaning
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.6, phastCons 1
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% African / African-American · 8/74,798 alleles

Filtering AF 0.00529% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00248% 40/1,612,476 alleles · ultra-rare exomes 27/1,460,420 · genomes 13/152,056 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0107%	9,350
South Asian	0.00329%	30,355
European (non-Finnish)	0.00229%	43,671
East Asian	0.00223%	44,882
Finnishnot grpmax-eligible	0.00157%	63,666

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.Arg15Trp
Coding: c.43C>T
MANE Select: NM_001394062 · reported on NM_012090
Type: single nucleotide variant
Location: chr1:39084261 (GRCh38)
Gene constraint: LOEUF 0.238 · pLI 1.00 (gnomAD)
Residue 15: the 'disordered' region; the 'actin-binding' region

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-arg15trp (accessed [today's date]).

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