Is SRRM2 p.Pro985Arg (c.2954C>G) pathogenic?

SRRM2 p.Pro985Arg (c.2954C>G) is classified Uncertain significance in SRRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-02). AlphaMissense: likely benign (0.1125); Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with SRRM2 p.Pro985Arg (c.2954C>G)?

SRRM2 p.Pro985Arg (c.2954C>G) is associated with Inborn genetic diseases (ClinVar).

How common is SRRM2 p.Pro985Arg (c.2954C>G) in the general population?

SRRM2 p.Pro985Arg (c.2954C>G) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about SRRM2 p.Pro985Arg (c.2954C>G)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

SRRM2 p.Pro985Arg

c.2954C>G · rs771368757 · VCV2215507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign
REVEL	0.054	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 0.25	GERP 1.2
Regional constraint	o/e 1.38	unconstrained · MANE · 11 kb · p 1.5e-90 · regional, not allelic
Overall
CADD	14.13	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

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,024 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00105% 17/1,614,170 alleles · very rare exomes 17/1,461,884 · genomes 0/152,286 · joint denominator

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: SRRM2
Protein: p.Pro985Arg
Coding: c.2954C>G
MANE Select: NM_016333
dbSNP: rs771368757
Type: single nucleotide variant
Location: chr16:2763482 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 985: 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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SRRM2 p.Arg1836Ter Pathogenic ★★ same condition
SRRM2 p.Arg280Ter Pathogenic ★★ same condition
SRRM2 p.Ala2245Val Uncertain significance ★★ same condition
SRRM2 p.Arg1213Gly Uncertain significance ★★ ⚠ same condition
SRRM2 p.Arg1723Lys Uncertain significance ★★ ⚠ same condition
SRRM2 p.Arg1971Gln Uncertain significance ★★ same condition
SRRM2 p.Arg530Gln Uncertain significance ★★ ⚠ same condition
SRRM2 p.Arg623His Uncertain significance ★★ same condition

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-pro985arg (accessed [today's date]).

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