Is EID1 p.Pro57Arg (c.170C>G) pathogenic?

EID1 p.Pro57Arg (c.170C>G) is classified Uncertain significance in EID1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-06). AlphaMissense: likely benign (0.199); Very rare (popmax 0.00212%, nfe).

How common is EID1 p.Pro57Arg (c.170C>G) in the general population?

EID1 p.Pro57Arg (c.170C>G) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about EID1 p.Pro57Arg (c.170C>G)?

AlphaMissense predicts likely benign (score 0.199) — an in-silico prediction, not a clinical call.

EID1 p.Pro57Arg

c.170C>G · rs761401009 · VCV2410834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.199 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.199	likely benign
REVEL	0.126	moderately benign-leaning
SaProt	LLR -6.90	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 2.6, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 471 bp · p 0.022 · regional, not allelic
Overall
CADD	23.4	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 0.00212% European (non-Finnish) · 25/1,179,662 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00167% 27/1,613,422 alleles · very rare exomes 21/1,461,248 · genomes 6/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00212%	47,187
Finnishnot grpmax-eligible	0.00156%	63,944
African / African-American	0.00133%	74,918

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: EID1
Protein: p.Pro57Arg
Coding: c.170C>G
MANE Select: NM_014335
dbSNP: rs761401009
Type: single nucleotide variant
Location: chr15:48878346 (GRCh38)
Gene constraint: LOEUF 0.544 · pLI 0.94 (gnomAD)
Structure: AlphaFold pLDDT 56.72 · 1 PDB
Residue 57: the 'disordered' region; the 'interaction with nr0b2' region

Full EID1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EID1 p.Ala131Pro Uncertain significance ★ ⚠ same type
EID1 p.Ala5Thr Uncertain significance ★ ⚠ same type
EID1 p.Ala81Thr Uncertain significance ★ ⚠ same type
EID1 p.Asn172Ser Uncertain significance ★ ⚠ same type
EID1 p.Asn80Lys Uncertain significance ★ ⚠ same type
EID1 p.Asp92Glu Uncertain significance ★ ⚠ same type
EID1 p.Gln51Arg Uncertain significance ★ ⚠ same type
EID1 p.Glu129Gln 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/eid1-p-pro57arg (accessed [today's date]).

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