Is MAK p.Pro309= (c.927A>C) pathogenic?

MAK p.Pro309= (c.927A>C) is classified Likely benign in MAK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-26). Very rare (popmax 0.00133%, afr).

How common is MAK p.Pro309= (c.927A>C) in the general population?

MAK p.Pro309= (c.927A>C) is very rare (popmax 0.00133%, afr) (gnomAD).

MAK p.Pro309=

c.927A>C · rs1775544515 · VCV2893116

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP -3.3
Overall
CADD	0.162	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,932 alleles

Overall 0.000124% 2/1,614,094 alleles · very rare exomes 1/1,461,892 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
African / African-Americangrpmax	0.00133%	74,932

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MAK
Protein: p.Pro309=
Coding: c.927A>C
MANE Select: NM_001242957
dbSNP: rs1775544515
Type: single nucleotide variant
Location: chr6:10796214 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.74

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

Similar variants

MAK c.101+1G>A Likely pathogenic ★★ same type
MAK c.156+2T>C Likely pathogenic ★★ same type
MAK c.831+1G>C Likely pathogenic ★★ same type
MAK c.832-1G>C Likely pathogenic ★★ same type
MAK p.Arg166His Pathogenic ★★ same type
MAK p.Arg272Ter Pathogenic/Likely pathogenic ★★ same type
MAK p.Arg3Ter Pathogenic/Likely pathogenic ★★ same type
MAK p.Asn130His Likely pathogenic ★★ 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/mak-p-pro309 (accessed [today's date]).

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