Is SRRM2 p.Ser671Phe (c.2012C>T) pathogenic?

SRRM2 p.Ser671Phe (c.2012C>T) is classified Uncertain significance in SRRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-30). AlphaMissense: likely pathogenic (0.8126); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with SRRM2 p.Ser671Phe (c.2012C>T)?

SRRM2 p.Ser671Phe (c.2012C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SRRM2 p.Ser671Phe (c.2012C>T) in the general population?

SRRM2 p.Ser671Phe (c.2012C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRRM2 p.Ser671Phe (c.2012C>T)?

AlphaMissense predicts likely pathogenic (score 0.8126) — an in-silico prediction, not a clinical call.

SRRM2 p.Ser671Phe

c.2012C>T · rs559774892 · VCV2330190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8126 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8126	likely pathogenic · top 9% in SRRM2
REVEL	0.208	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 3.6, phastCons 1
Regional constraint	o/e 1.38	unconstrained · MANE · 11 kb · p 1.5e-90 · 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

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.Ser671Phe
Coding: c.2012C>T
MANE Select: NM_016333
dbSNP: rs559774892
Type: single nucleotide variant
Location: chr16:2762540 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 671: 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-ser671phe (accessed [today's date]).

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