Is SRRM2 p.Arg705Ser (c.2115A>C) pathogenic?

SRRM2 p.Arg705Ser (c.2115A>C) is classified Likely benign in SRRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-13). AlphaMissense: likely pathogenic (0.7593); Rare (popmax 0.356%, afr); Associated with Inborn genetic diseases.

What condition is associated with SRRM2 p.Arg705Ser (c.2115A>C)?

SRRM2 p.Arg705Ser (c.2115A>C) is associated with Inborn genetic diseases (ClinVar).

How common is SRRM2 p.Arg705Ser (c.2115A>C) in the general population?

SRRM2 p.Arg705Ser (c.2115A>C) is rare (popmax 0.356%, afr) (gnomAD).

What do computational predictors say about SRRM2 p.Arg705Ser (c.2115A>C)?

AlphaMissense predicts likely pathogenic (score 0.7593) — an in-silico prediction, not a clinical call.

SRRM2 p.Arg705Ser

c.2115A>C · VCV3322710

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7593 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.356%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7593	likely pathogenic
REVEL	0.191	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 1.7, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 11 kb · p 1.5e-90 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.356% African / African-American · 267/75,036 alleles

Filtering AF 0.321% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.307%

Overall 0.0203% 328/1,614,162 alleles · rare exomes 178/1,461,864 · genomes 150/152,298 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.356%	281
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0304%	3,290
Admixed American	0.0267%	3,752
South Asian	0.0022%	45,542
European (non-Finnish)	0.00186%	53,637

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.Arg705Ser
Coding: c.2115A>C
MANE Select: NM_016333
Type: single nucleotide variant
Location: chr16:2762643 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 705: 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-arg705ser (accessed [today's date]).

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