Is ECSIT p.Arg232Trp (c.694C>T) pathogenic?

ECSIT p.Arg232Trp (c.694C>T) is classified Uncertain significance in ECSIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: likely benign (0.1314); Ultra-rare (popmax 0.0209%, sas).

How common is ECSIT p.Arg232Trp (c.694C>T) in the general population?

ECSIT p.Arg232Trp (c.694C>T) is ultra-rare (popmax 0.0209%, sas) (gnomAD).

What do computational predictors say about ECSIT p.Arg232Trp (c.694C>T)?

AlphaMissense predicts likely benign (score 0.1314) — an in-silico prediction, not a clinical call.

ECSIT p.Arg232Trp

c.694C>T · VCV4016117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1314 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1314	likely benign
REVEL	0.535	indeterminate
SaProt	LLR -9.75	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.4	GERP 0.33, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 13 kb · p 0.11 · regional, not allelic
Overall
CADD	23.2	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 0.0209% South Asian · 19/91,094 alleles

Filtering AF 0.0136% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.00273% 44/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0209%	4,794
African / African-American	0.00267%	37,478
European (non-Finnish)	0.00186%	53,638
Remaining individualsnot grpmax-eligible	0.0016%	62,490

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.Arg232Trp
Coding: c.694C>T
MANE Select: NM_016581
Type: single nucleotide variant
Location: chr19:11513100 (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.Arg115Cys Uncertain significance ★ ⚠ same type
ECSIT p.Arg118Trp Uncertain significance ★ ⚠ same type
ECSIT p.Arg11Gln 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-arg232trp (accessed [today's date]).

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