Is MPC1 p.Lys16Arg (c.47A>G) pathogenic?

MPC1 p.Lys16Arg (c.47A>G) is classified Uncertain significance in MPC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.0933); Ultra-rare (popmax 0.0259%, sas).

How common is MPC1 p.Lys16Arg (c.47A>G) in the general population?

MPC1 p.Lys16Arg (c.47A>G) is ultra-rare (popmax 0.0259%, sas) (gnomAD).

What do computational predictors say about MPC1 p.Lys16Arg (c.47A>G)?

AlphaMissense predicts likely benign (score 0.0933) — an in-silico prediction, not a clinical call.

MPC1 p.Lys16Arg

c.47A>G · VCV3397573

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0933 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0259%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0933	likely benign
REVEL	0.306	indeterminate
SaProt	LLR -6.73	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.4	GERP 2, phastCons 1
Regional constraint	o/e 1.20	unconstrained · MANE · 13 kb · p 0.24 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.0259% South Asian · 23/88,740 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.015%

Overall 0.0015% 24/1,597,756 alleles · ultra-rare exomes 23/1,445,554 · genomes 1/152,202 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0259%	3,858
Remaining individualsnot grpmax-eligible	0.00162%	61,842

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: MPC1
Protein: p.Lys16Arg
Coding: c.47A>G
MANE Select: NM_016098
Type: single nucleotide variant
Location: chr6:166382830 (GRCh38)
Gene constraint: LOEUF 0.919 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 92.85 · 13 PDB

Full MPC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MPC1 p.Arg76Gln Uncertain significance ★★ ⚠ same type
MPC1 p.Glu102Lys Uncertain significance ★★ ⚠ same type
MPC1 p.Thr106Met Uncertain significance ★★ ⚠ same type
MPC1 c.72-8C>T Likely benign ★★ same type
MPC1 p.Ala10= Benign/Likely benign ★★ same type
MPC1 p.His101= Benign ★★ same type
MPC1 p.Leu36Ile Benign ★★ same type
MPC1 p.Ala70Thr 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/mpc1-p-lys16arg (accessed [today's date]).

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