Is ECI1 p.Pro214Ser (c.640C>T) pathogenic?

ECI1 p.Pro214Ser (c.640C>T) is classified Uncertain significance in ECI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-06). AlphaMissense: likely benign (0.2838); Absent from gnomAD v4.1.

How common is ECI1 p.Pro214Ser (c.640C>T) in the general population?

ECI1 p.Pro214Ser (c.640C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ECI1 p.Pro214Ser (c.640C>T)?

AlphaMissense predicts likely benign (score 0.2838) — an in-silico prediction, not a clinical call.

ECI1 p.Pro214Ser

c.640C>T · VCV3843315

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2838 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2838	likely benign
REVEL	0.522	indeterminate
SaProt	LLR -5.81	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 12	GERP 2.2, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 12 kb · p 0.1 · regional, not allelic
Overall
CADD	19.74	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ECI1
Protein: p.Pro214Ser
Coding: c.640C>T
MANE Select: NM_001919
Type: single nucleotide variant
Location: chr16:2243148 (GRCh38)
Gene constraint: LOEUF 1.485 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.43 · 1 PDB
Residue 214: an α-helix

Full ECI1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECI1 p.Pro214Leu Uncertain significance ★ ⚠ same residue
ECI1 p.Thr76Met Benign ★★ same type
ECI1 p.Ala119Thr Uncertain significance ★ ⚠ same type
ECI1 p.Ala185Ser Uncertain significance ★ ⚠ same type
ECI1 p.Ala19Ser Uncertain significance ★ ⚠ same type
ECI1 p.Ala201Val Uncertain significance ★ ⚠ same type
ECI1 p.Ala202Val Uncertain significance ★ same type
ECI1 p.Ala2Val 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/eci1-p-pro214ser (accessed [today's date]).

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