Is ESX1 p.Pro334Gln (c.1001C>A) pathogenic?

ESX1 p.Pro334Gln (c.1001C>A) is classified Uncertain significance in ESX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: likely benign (0.1684); Absent from gnomAD v4.1.

How common is ESX1 p.Pro334Gln (c.1001C>A) in the general population?

ESX1 p.Pro334Gln (c.1001C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESX1 p.Pro334Gln (c.1001C>A)?

AlphaMissense predicts likely benign (score 0.1684) — an in-silico prediction, not a clinical call.

ESX1 p.Pro334Gln

c.1001C>A · rs1350960452 · VCV2297709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1684 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 930,168)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1684	likely benign
REVEL	0.156	moderately benign-leaning
SaProt	LLR -13.78	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.73	GERP 0.45
Regional constraint	o/e 0.40	unconstrained · MANE · 310 bp · p 9.9e-11 · regional, not allelic
Overall
CADD	9.262	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

No allele count reported in gnomAD v4.1 (AN 930,168). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ESX1
Protein: p.Pro334Gln
Coding: c.1001C>A
MANE Select: NM_153448
dbSNP: rs1350960452
Type: single nucleotide variant
Location: chrX:104250448 (GRCh38)
Structure: AlphaFold pLDDT 62.35
Residue 334: the '15 x 9 aa tandem repeats of p-p-x-x-p-x-p-p-x' region

Full ESX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ESX1 p.Pro320Arg Benign ★★ same type
ESX1 p.Trp297Gly Likely benign ★★ same type
ESX1 p.Pro365Arg Likely pathogenic ★ ⚠ same type
ESX1 p.Ala292Val Uncertain significance ★ ⚠ same type
ESX1 p.Ala301Thr Uncertain significance ★ ⚠ same type
ESX1 p.Ala319Val Uncertain significance ★ ⚠ same type
ESX1 p.Ala337Glu Uncertain significance ★ ⚠ same type
ESX1 p.Ala402Val 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/esx1-p-pro334gln (accessed [today's date]).

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