Is MAP3K19 p.Ala115Val (c.344C>T) pathogenic?

MAP3K19 p.Ala115Val (c.344C>T) is classified Uncertain significance in MAP3K19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-20). AlphaMissense: likely benign (0.0953); Very rare (popmax 0.000678%, nfe).

How common is MAP3K19 p.Ala115Val (c.344C>T) in the general population?

MAP3K19 p.Ala115Val (c.344C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

What do computational predictors say about MAP3K19 p.Ala115Val (c.344C>T)?

AlphaMissense predicts likely benign (score 0.0953) — an in-silico prediction, not a clinical call.

MAP3K19 p.Ala115Val

c.344C>T · rs769086800 · VCV2302760

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0953	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -5.83	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 0.28	GERP -2.1
Regional constraint	o/e 0.94	unconstrained · MANE · 60 kb · p 0.01 · regional, not allelic
Overall
CADD	1.529	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 0.000678% European (non-Finnish) · 8/1,179,988 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,768 alleles · very rare exomes 8/1,461,474 · genomes 0/152,294 · 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: MAP3K19
Protein: p.Ala115Val
Coding: c.344C>T
MANE Select: NM_025052
dbSNP: rs769086800
Type: single nucleotide variant
Location: chr2:134998968 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 44.13

Full MAP3K19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

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MAP3K19 p.Arg1185His Uncertain significance ★ ⚠ same type
MAP3K19 p.Arg1272Gly Uncertain significance ★ same type
MAP3K19 p.Arg1283Gln Uncertain significance ★ ⚠ same type
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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/map3k19-p-ala115val (accessed [today's date]).

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