Is ESPL1 p.Arg596Gln (c.1787G>A) pathogenic?

ESPL1 p.Arg596Gln (c.1787G>A) is classified Benign in ESPL1 (ClinVar, Single submitter, 2 submitters; last evaluated 2017-12-28). AlphaMissense: likely benign (0.1106); Low-frequency (popmax 1.57%, afr).

How common is ESPL1 p.Arg596Gln (c.1787G>A) in the general population?

ESPL1 p.Arg596Gln (c.1787G>A) is low-frequency (popmax 1.57%, afr) (gnomAD).

What do computational predictors say about ESPL1 p.Arg596Gln (c.1787G>A)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

ESPL1 p.Arg596Gln

c.1787G>A · rs143192971 · VCV732991

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.57%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -4.70	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 8.5	GERP -0.21, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 6.3e-24 · regional, not allelic
Overall
CADD	24.0	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

Grpmax group 1.57% African / African-American · 1,176/75,044 alleles

Filtering AF 1.49% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.46%

Overall 0.0842% 1,359/1,613,202 alleles · low-frequency exomes 701/1,460,898 · genomes 658/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.57%	64
Remaining individualsnot grpmax-eligible	0.0832%	1,202
Admixed American	0.075%	1,334
Middle Eastern	0.0495%	2,020
European (non-Finnish)	0.00686%	14,568
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
South Asian	0.0011%	91,078

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: ESPL1
Protein: p.Arg596Gln
Coding: c.1787G>A
MANE Select: NM_012291
dbSNP: rs143192971
Type: single nucleotide variant
Location: chr12:53276706 (GRCh38)
Gene constraint: LOEUF 0.292 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.67 · 9 PDB
Residue 596: a β-strand

Full ESPL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ESPL1 p.Arg596Leu Uncertain significance ★ ⚠ same residue
ESPL1 c.6162-10C>T Benign ★★ same type
ESPL1 p.Ala1462Thr Benign ★★ same type
ESPL1 p.Asn918Ser Benign ★★ same type
ESPL1 p.Gly1337Val Benign ★★ same type
ESPL1 p.Ile1488Asn Benign ★★ same type
ESPL1 p.Ser969= Benign ★★ same type
ESPL1 p.Thr2073Met Likely benign ★★ ⚠ 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/espl1-p-arg596gln (accessed [today's date]).

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