Is ECSIT p.Arg115Cys (c.343C>T) pathogenic?

ECSIT p.Arg115Cys (c.343C>T) is classified Uncertain significance in ECSIT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-30). AlphaMissense: likely benign (0.1727); Ultra-rare (popmax 0.029%, eas).

How common is ECSIT p.Arg115Cys (c.343C>T) in the general population?

ECSIT p.Arg115Cys (c.343C>T) is ultra-rare (popmax 0.029%, eas) (gnomAD).

What do computational predictors say about ECSIT p.Arg115Cys (c.343C>T)?

AlphaMissense predicts likely benign (score 0.1727) — an in-silico prediction, not a clinical call.

ECSIT p.Arg115Cys

c.343C>T · VCV3506560

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.029%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1727	likely benign
REVEL	0.683	pathogenic-leaning
SaProt	LLR -11.00	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.62, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 13 kb · p 0.11 · regional, not allelic
Overall
CADD	26.7	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 0.029% East Asian · 13/44,884 alleles

Filtering AF 0.0171% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.00223% 36/1,614,206 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.029%	3,453
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,837
African / African-American	0.00266%	37,534
European (non-Finnish)	0.00144%	69,414

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: ECSIT
Protein: p.Arg115Cys
Coding: c.343C>T
MANE Select: NM_016581
Type: single nucleotide variant
Location: chr19:11513975 (GRCh38)
Gene constraint: LOEUF 1.033 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.35 · 1 PDB

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

Similar variants

ECSIT p.Ala45Val Uncertain significance ★ ⚠ same type
ECSIT p.Ala47Ser Uncertain significance ★ ⚠ same type
ECSIT p.Ala79Val Uncertain significance ★ ⚠ same type
ECSIT p.Ala97Val Uncertain significance ★ ⚠ same type
ECSIT p.Arg104Trp Uncertain significance ★ ⚠ same type
ECSIT p.Arg118Trp Uncertain significance ★ ⚠ same type
ECSIT p.Arg11Gln Uncertain significance ★ ⚠ same type
ECSIT p.Arg124Gln 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/ecsit-p-arg115cys (accessed [today's date]).

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