Is ESF1 p.Pro670Arg (c.2009C>G) pathogenic?

ESF1 p.Pro670Arg (c.2009C>G) is classified Uncertain significance in ESF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-01). AlphaMissense: ambiguous (0.3491); Absent from gnomAD v4.1.

How common is ESF1 p.Pro670Arg (c.2009C>G) in the general population?

ESF1 p.Pro670Arg (c.2009C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESF1 p.Pro670Arg (c.2009C>G)?

AlphaMissense predicts ambiguous (score 0.3491) — an in-silico prediction, not a clinical call.

ESF1 p.Pro670Arg

c.2009C>G · VCV3846206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3491 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3491	ambiguous
REVEL	0.333	indeterminate
SaProt	LLR -14.21	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 68 kb · p 0.033 · regional, not allelic
Overall
CADD	29.0	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

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: ESF1
Protein: p.Pro670Arg
Coding: c.2009C>G
MANE Select: NM_001276380
Type: single nucleotide variant
Location: chr20:13728407 (GRCh38)
Gene constraint: LOEUF 0.854 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.81

Full ESF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NDUFAF5 c.-208C>T Benign ★★ same type
ESF1 p.Ala120Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala303Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala412Ser Uncertain significance ★ ⚠ same type
ESF1 p.Ala651Ser Uncertain significance ★ ⚠ same type
ESF1 p.Ala651Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala653Thr Uncertain significance ★ ⚠ same type
ESF1 p.Ala709Val 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/esf1-p-pro670arg (accessed [today's date]).

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