Is MAK p.Asp329His (c.985G>C) pathogenic?

MAK p.Asp329His (c.985G>C) is classified Uncertain significance in MAK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-21). AlphaMissense: likely benign (0.1131); Absent from gnomAD v4.1.

How common is MAK p.Asp329His (c.985G>C) in the general population?

MAK p.Asp329His (c.985G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAK p.Asp329His (c.985G>C)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

MAK p.Asp329His

c.985G>C · VCV4973712

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.144	moderately benign-leaning
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 0.8, phastCons 0.89
Regional constraint	o/e 0.90	unconstrained · MANE · 66 kb · p 0.0057 · regional, not allelic
Overall
CADD	19.31	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAK
Protein: p.Asp329His
Coding: c.985G>C
MANE Select: NM_001242957
Type: single nucleotide variant
Location: chr6:10796156 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.74
Residue 329: the 'disordered' region; a UniProt-annotated variant site (in)

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

Similar variants

MAK p.Asp329Asn Uncertain significance ★★ ⚠ same residue
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

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-asp329his (accessed [today's date]).

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