Is MLST8 p.Pro5Ser (c.13C>T) pathogenic?

MLST8 p.Pro5Ser (c.13C>T) is classified Uncertain significance in MLST8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.0592); Ultra-rare (popmax 0.0157%, eas).

How common is MLST8 p.Pro5Ser (c.13C>T) in the general population?

MLST8 p.Pro5Ser (c.13C>T) is ultra-rare (popmax 0.0157%, eas) (gnomAD).

What do computational predictors say about MLST8 p.Pro5Ser (c.13C>T)?

AlphaMissense predicts likely benign (score 0.0592) — an in-silico prediction, not a clinical call.

MLST8 p.Pro5Ser

c.13C>T · rs760859672 · VCV2548990

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0592 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0157%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0592	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -4.58	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 3.3	GERP 2.3, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,788 bp · p 0.13 · regional, not allelic
Overall
CADD	21.5	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 0.0157% East Asian · 7/44,626 alleles

Filtering AF 0.00729% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00517%

Overall 0.000499% 8/1,602,622 alleles · ultra-rare exomes 7/1,450,346 · genomes 1/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0157%	6,375
Remaining individualsnot grpmax-eligible	0.00162%	61,914

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.Pro5Ser
Coding: c.13C>T
MANE Select: NM_022372
dbSNP: rs760859672
Type: single nucleotide variant
Location: chr16:2206098 (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-pro5ser (accessed [today's date]).

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