Is MAPK14 p.His312= (c.936C>T) pathogenic?

MAPK14 p.His312= (c.936C>T) is classified Benign in MAPK14 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-19). Low-frequency (popmax 4.59%, afr).

How common is MAPK14 p.His312= (c.936C>T) in the general population?

MAPK14 p.His312= (c.936C>T) is low-frequency (popmax 4.59%, afr) (gnomAD).

MAPK14 p.His312=

c.936C>T · rs28763973 · VCV782474

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 4.59%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.112	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.8
Overall
CADD	1.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.59% African / African-American · 3,439/74,846 alleles

Filtering AF 4.47% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.41%

Overall 0.25% 4,013/1,606,390 alleles · low-frequency exomes 1,994/1,454,080 · genomes 2,019/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.59%	22
Admixed American	0.407%	245
Remaining individualsnot grpmax-eligible	0.275%	364
Middle Eastern	0.182%	550
South Asian	0.0394%	2,535
Finnishnot grpmax-eligible	0.0141%	7,106
European (non-Finnish)	0.00901%	11,098
East Asian	0.00224%	44,636

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: MAPK14
Protein: p.His312=
Coding: c.936C>T
MANE Select: NM_139012
dbSNP: rs28763973
Type: single nucleotide variant
Location: chr6:36107549 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI 0.91 (gnomAD)
Structure: AlphaFold pLDDT 89.91 · 267 PDB

Full MAPK14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK14 c.763-2308A>G Uncertain significance ★ same type
MAPK14 c.763-2312A>G Uncertain significance ★ same type
MAPK14 c.763-2316G>A Uncertain significance ★ same type
MAPK14 c.763-2341C>G Uncertain significance ★ same type
MAPK14 c.763-2356G>A Uncertain significance ★ same type
MAPK14 p.Ala304Val Uncertain significance ★ ⚠ same type
MAPK14 p.Ala41Thr Uncertain significance ★ ⚠ same type
MAPK14 p.Arg10Pro 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/mapk14-p-his312 (accessed [today's date]).

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