Is MTSS2 p.Pro710Thr (c.2128C>A) pathogenic?

MTSS2 p.Pro710Thr (c.2128C>A) is classified Likely benign in MTSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-04-01). AlphaMissense: likely benign (0.0719); Rare (popmax 0.356%, sas).

How common is MTSS2 p.Pro710Thr (c.2128C>A) in the general population?

MTSS2 p.Pro710Thr (c.2128C>A) is rare (popmax 0.356%, sas) (gnomAD).

What do computational predictors say about MTSS2 p.Pro710Thr (c.2128C>A)?

AlphaMissense predicts likely benign (score 0.0719) — an in-silico prediction, not a clinical call.

MTSS2 p.Pro710Thr

c.2128C>A · VCV4872642

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0719 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.356%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0719	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -7.11	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.6	GERP -0.7, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 14 kb · p 1e-09 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.356% South Asian · 290/81,468 alleles

Filtering AF 0.322% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.309%

Overall 0.0227% 345/1,521,172 alleles · rare exomes 321/1,368,854 · genomes 24/152,318 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.356%	281
Middle Eastern	0.204%	490
Remaining individualsnot grpmax-eligible	0.0305%	3,276
European (non-Finnish)	0.00247%	40,562

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: MTSS2
Protein: p.Pro710Thr
Coding: c.2128C>A
MANE Select: NM_138383
Type: single nucleotide variant
Location: chr16:70663793 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.75
Residue 710: the 'disordered' region

Full MTSS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MTSS2 p.Arg671Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
MTSS2 p.Arg734Cys Uncertain significance ★★ ⚠ same type
MTSS2 p.Val368Ile Uncertain significance ★★ ⚠ same type
MTSS2 p.Pro712= Likely benign ★★ same type
MTSS2 p.Ser252= Benign ★★ same type
MTSS2 p.Thr181= Likely benign ★★ same type
MTSS2 c.291-6C>G Uncertain significance ★ same type
MTSS2 c.291-8C>T 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/mtss2-p-pro710thr (accessed [today's date]).

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