Is MACF1 p.Ala5250Ser (c.15748G>T) pathogenic?

MACF1 p.Ala5250Ser (c.15748G>T) is classified Likely benign in MACF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: likely benign (0.0723); Ultra-rare (popmax 0.011%, sas); Associated with Inborn genetic diseases.

What condition is associated with MACF1 p.Ala5250Ser (c.15748G>T)?

MACF1 p.Ala5250Ser (c.15748G>T) is associated with Inborn genetic diseases (ClinVar).

How common is MACF1 p.Ala5250Ser (c.15748G>T) in the general population?

MACF1 p.Ala5250Ser (c.15748G>T) is ultra-rare (popmax 0.011%, sas) (gnomAD).

What do computational predictors say about MACF1 p.Ala5250Ser (c.15748G>T)?

AlphaMissense predicts likely benign (score 0.0723) — an in-silico prediction, not a clinical call.

MACF1 p.Ala5250Ser

c.15748G>T · VCV3292487

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0723 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.011%, sas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0723	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 1.3, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 93 kb · p 4.8e-14 · regional, not allelic
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A5255S vs ClinVar A5250S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.011% South Asian · 10/90,980 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00454%

Overall 0.00062% 10/1,613,480 alleles · ultra-rare exomes 10/1,461,168 · genomes 0/152,312 · joint denominator

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.Ala5250Ser
Coding: c.15748G>T
MANE Select: NM_001394062
Type: single nucleotide variant
Location: chr1:39388590 (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-ala5250ser (accessed [today's date]).

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