Is MAPK6 p.Ser571Arg (c.1713C>A) pathogenic?

MAPK6 p.Ser571Arg (c.1713C>A) is classified Uncertain significance in MAPK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-25). AlphaMissense: ambiguous (0.4521); Very rare (popmax 0.0011%, sas).

How common is MAPK6 p.Ser571Arg (c.1713C>A) in the general population?

MAPK6 p.Ser571Arg (c.1713C>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about MAPK6 p.Ser571Arg (c.1713C>A)?

AlphaMissense predicts ambiguous (score 0.4521) — an in-silico prediction, not a clinical call.

MAPK6 p.Ser571Arg

c.1713C>A · VCV4051600

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4521 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4521	ambiguous
REVEL	0.242	benign-leaning
SaProt	LLR -7.76	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 6,229 bp · p 0.8 · regional, not allelic
Overall
CADD	21.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,784 alleles

Overall 6.21e-05% 1/1,611,196 alleles · very rare exomes 1/1,458,966 · genomes 0/152,230 · 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: MAPK6
Protein: p.Ser571Arg
Coding: c.1713C>A
MANE Select: NM_002748
Type: single nucleotide variant
Location: chr15:52064547 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 58.61 · 4 PDB

Full MAPK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK6 p.Ala218Gly Uncertain significance ★ ⚠ same type
MAPK6 p.Ala515Gly Uncertain significance ★ ⚠ same type
MAPK6 p.Ala515Ser Uncertain significance ★ ⚠ same type
MAPK6 p.Ala695Thr Uncertain significance ★ ⚠ same type
MAPK6 p.Arg256His Uncertain significance ★ ⚠ same type
MAPK6 p.Arg406Gln Uncertain significance ★ ⚠ same type
MAPK6 p.Arg406Trp Uncertain significance ★ ⚠ same type
MAPK6 p.Arg449Lys Uncertain significance ★ ⚠ 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/mapk6-p-ser571arg (accessed [today's date]).

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