Is SRRM2 p.Pro765Leu (c.2294C>T) pathogenic?

SRRM2 p.Pro765Leu (c.2294C>T) is classified Uncertain significance in SRRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-15). AlphaMissense: likely benign (0.2435); Absent from gnomAD v4.1.

How common is SRRM2 p.Pro765Leu (c.2294C>T) in the general population?

SRRM2 p.Pro765Leu (c.2294C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRRM2 p.Pro765Leu (c.2294C>T)?

AlphaMissense predicts likely benign (score 0.2435) — an in-silico prediction, not a clinical call.

SRRM2 p.Pro765Leu

c.2294C>T · VCV4928175

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2435 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.2435	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 2.2, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 11 kb · p 1.5e-90 · regional, not allelic
Overall
CADD	21.9	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 is an independent agreement signal.

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: SRRM2
Protein: p.Pro765Leu
Coding: c.2294C>T
MANE Select: NM_016333
Type: single nucleotide variant
Location: chr16:2762822 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 765: the 'disordered' region; a UniProt-annotated variant site (in mrd72; likely pathogenic)

Full SRRM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SRRM2 p.Pro765= Likely benign ★ same residue
SRRM2 p.Arg1836Ter Pathogenic ★★ same type
SRRM2 p.Arg1875Ter Pathogenic/Likely pathogenic ★★ same type
SRRM2 p.Arg280Ter Pathogenic ★★ same type
SRRM2 p.Arg628Ter Pathogenic ★★ same type
SRRM2 p.Ala2245Val Uncertain significance ★★ same type
SRRM2 p.Arg1213Gly Uncertain significance ★★ ⚠ same type
SRRM2 p.Arg1723Lys 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/srrm2-p-pro765leu (accessed [today's date]).

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