Is MLH3 p.Arg600= (c.1798C>A) pathogenic?

MLH3 p.Arg600= (c.1798C>A) is classified Likely benign in MLH3 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-11). Very rare (popmax 0.00223%, eas).

How common is MLH3 p.Arg600= (c.1798C>A) in the general population?

MLH3 p.Arg600= (c.1798C>A) is very rare (popmax 0.00223%, eas) (gnomAD).

MLH3 p.Arg600=

c.1798C>A · rs927878214 · VCV1780297

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5	GERP 0.83, phastCons 1
Overall
CADD	6.225	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,858 alleles

Overall 6.2e-05% 1/1,612,774 alleles · very rare exomes 1/1,460,596 · genomes 0/152,178 · 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: MLH3
Protein: p.Arg600=
Coding: c.1798C>A
MANE Select: NM_001040108
dbSNP: rs927878214
Type: single nucleotide variant
Location: chr14:75047858 (GRCh38)
Gene constraint: LOEUF 0.735 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.14
Residue 600: a UniProt-annotated variant site (in)

Full MLH3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MLH3 p.Arg600Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
MLH3 p.Arg600Leu Uncertain significance ★ ⚠ same residue
MLH3 p.Arg600Ter Conflicting classifications of pathogenicity ★ same residue
MLH3 p.Gln1360Ter Pathogenic ★★ same type
MLH3 p.Gln423Ter Pathogenic ★★ same type
MLH3 p.Ser626Ter Pathogenic ★★ same type
MLH3 p.Tyr441Ter Pathogenic ★★ same type
MLH3 c.3280+4A>G 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/mlh3-p-arg600 (accessed [today's date]).

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