Is ECSIT p.Arg124Gln (c.371G>A) pathogenic?

ECSIT p.Arg124Gln (c.371G>A) is classified Uncertain significance in ECSIT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). AlphaMissense: likely benign (0.0858); Ultra-rare (popmax 0.098%, eas).

How common is ECSIT p.Arg124Gln (c.371G>A) in the general population?

ECSIT p.Arg124Gln (c.371G>A) is ultra-rare (popmax 0.098%, eas) (gnomAD).

What do computational predictors say about ECSIT p.Arg124Gln (c.371G>A)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

ECSIT p.Arg124Gln

c.371G>A · VCV4662983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.098%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -7.83	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 0.81	GERP 0.45, phastCons 0.27
Regional constraint	o/e 0.93	unconstrained · MANE · 13 kb · p 0.11 · regional, not allelic
Overall
CADD	23.0	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 0.098% East Asian · 44/44,896 alleles

Filtering AF 0.075% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0668%

Overall 0.00322% 52/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.098%	1,020
South Asian	0.0022%	45,544
African / African-American	0.00133%	74,932
European (non-Finnish)	0.000424%	236,009

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.Arg124Gln
Coding: c.371G>A
MANE Select: NM_016581
Type: single nucleotide variant
Location: chr19:11513947 (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.Arg124Trp Uncertain significance ★ ⚠ same residue
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

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-arg124gln (accessed [today's date]).

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