Is MLST8 p.Arg270= (c.810C>T) pathogenic?

MLST8 p.Arg270= (c.810C>T) is classified Likely benign in MLST8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). Ultra-rare (popmax 0.0147%, afr).

How common is MLST8 p.Arg270= (c.810C>T) in the general population?

MLST8 p.Arg270= (c.810C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

MLST8 p.Arg270=

c.810C>T · VCV3771019

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4	GERP -3.9
Overall
CADD	0.231	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/75,012 alleles

Filtering AF 0.00814% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00229% 37/1,612,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,819
Remaining individualsnot grpmax-eligible	0.00801%	12,491
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,564
Admixed American	0.00334%	29,964
South Asian	0.0022%	45,544
European (non-Finnish)	0.00136%	73,737

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: MLST8
Protein: p.Arg270=
Coding: c.810C>T
MANE Select: NM_022372
Type: single nucleotide variant
Location: chr16:2208561 (GRCh38)
Gene constraint: LOEUF 0.679 · pLI 0.02 (gnomAD)
Structure: AlphaFold pLDDT 92.15 · 45 PDB

Full MLST8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MLST8 p.Ala223Thr Uncertain significance ★ ⚠ same type
MLST8 p.Arg221Cys Uncertain significance ★ same type
MLST8 p.Arg227Cys Uncertain significance ★ ⚠ same type
MLST8 p.Arg227His Uncertain significance ★ ⚠ same type
MLST8 p.Arg25His Uncertain significance ★ ⚠ same type
MLST8 p.Arg66Leu Uncertain significance ★ ⚠ same type
MLST8 p.Asn132Lys Uncertain significance ★ ⚠ same type
MLST8 p.Asn321Ser 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/mlst8-p-arg270 (accessed [today's date]).

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