Is MTSS2 p.Ala577Val (c.1730C>T) pathogenic?

MTSS2 p.Ala577Val (c.1730C>T) is classified Benign in MTSS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-07-01). AlphaMissense: likely benign (0.1544); Low-frequency (popmax 1.3%, sas).

How common is MTSS2 p.Ala577Val (c.1730C>T) in the general population?

MTSS2 p.Ala577Val (c.1730C>T) is low-frequency (popmax 1.3%, sas) (gnomAD).

What do computational predictors say about MTSS2 p.Ala577Val (c.1730C>T)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

MTSS2 p.Ala577Val

c.1730C>T · VCV3770567

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.3%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.43	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 7.4	GERP -3.8, phastCons 1
Regional constraint	o/e 1.22	unconstrained · MANE · 14 kb · p 1e-09 · regional, not allelic
Overall
CADD	24.9	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 1.3% South Asian · 1,174/90,650 alleles

Filtering AF 1.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.25%

Overall 1.12% 17,896/1,599,090 alleles · low-frequency exomes 16,797/1,446,800 · genomes 1,099/152,290 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.3%	77
European (non-Finnish)	1.28%	78
Finnishnot grpmax-eligible	1.07%	93
Remaining individualsnot grpmax-eligible	0.812%	123
Admixed American	0.624%	160
Middle Eastern	0.348%	287
Ashkenazi Jewishnot grpmax-eligible	0.239%	419
African / African-American	0.202%	496
Amishnot grpmax-eligible	0.11%	912
East Asian	0.00448%	22,344

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.Ala577Val
Coding: c.1730C>T
MANE Select: NM_138383
Type: single nucleotide variant
Location: chr16:70664191 (GRCh38)
Gene constraint: LOEUF 0.662 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.75
Residue 577: the 'disordered' region

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

Similar variants

MTSS2 p.Ala577Thr Uncertain significance ★ ⚠ same residue
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

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-ala577val (accessed [today's date]).

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