Is SRRM2 p.Ala1626Val (c.4877C>T) pathogenic?

SRRM2 p.Ala1626Val (c.4877C>T) is classified Uncertain significance in SRRM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0673); Ultra-rare (popmax 0.0164%, mid); Associated with Inborn genetic diseases.

What condition is associated with SRRM2 p.Ala1626Val (c.4877C>T)?

SRRM2 p.Ala1626Val (c.4877C>T) is associated with Inborn genetic diseases (ClinVar).

How common is SRRM2 p.Ala1626Val (c.4877C>T) in the general population?

SRRM2 p.Ala1626Val (c.4877C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about SRRM2 p.Ala1626Val (c.4877C>T)?

AlphaMissense predicts likely benign (score 0.0673) — an in-silico prediction, not a clinical call.

SRRM2 p.Ala1626Val

c.4877C>T · rs949284076 · VCV2600997

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0673 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0673	likely benign
REVEL	0.013	strongly 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 -0.4	GERP -3.6
Regional constraint	o/e 1.38	unconstrained · MANE · 11 kb · p 1.5e-90 · regional, not allelic
Overall
CADD	5.736	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000867% 14/1,614,064 alleles · ultra-rare exomes 12/1,461,892 · genomes 2/152,172 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Admixed American	0.00333%	30,005
African / African-American	0.00267%	37,454
European (non-Finnish)	0.000508%	196,674

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.Ala1626Val
Coding: c.4877C>T
MANE Select: NM_016333
dbSNP: rs949284076
Type: single nucleotide variant
Location: chr16:2765405 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 1626: 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-ala1626val (accessed [today's date]).

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