Is SRRT p.Arg354Trp (c.1060C>T) pathogenic?

SRRT p.Arg354Trp (c.1060C>T) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-09). AlphaMissense: ambiguous (0.4045); Absent from gnomAD v4.1; Associated with SRRT-related condition.

What condition is associated with SRRT p.Arg354Trp (c.1060C>T)?

SRRT p.Arg354Trp (c.1060C>T) is associated with SRRT-related condition (ClinVar).

How common is SRRT p.Arg354Trp (c.1060C>T) in the general population?

SRRT p.Arg354Trp (c.1060C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRRT p.Arg354Trp (c.1060C>T)?

AlphaMissense predicts ambiguous (score 0.4045) — an in-silico prediction, not a clinical call.

SRRT p.Arg354Trp

c.1060C>T · VCV3906927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4045 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

SRRT-related condition

Computational evidence

Protein change
AlphaMissense	0.4045	ambiguous
REVEL	0.158	moderately benign-leaning
SaProt	LLR -10.34	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -1.9, phastCons 0.006
Regional constraint	o/e 1.12	unconstrained · MANE · 784 bp · p 0.15 · regional, not allelic
Overall
CADD	19.7	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: SRRT
Protein: p.Arg354Trp
Coding: c.1060C>T
MANE Select: NM_015908
Type: single nucleotide variant
Location: chr7:100884941 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 354: the 'disordered' region

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

Disease context

SRRT-related condition

Similar variants

SRRT p.Arg354Gln Uncertain significance ★ ⚠ same residue
SRRT c.1042-18C>G Benign ★★ same type
SRRT c.1042-7C>T Benign ★★ same type
SRRT c.2556-9A>T Benign ★★ same type
SRRT p.Arg518= Benign ★★ same type
SRRT p.Glu205= Benign ★★ same type
SRRT p.Leu157= Benign ★★ same type
SRRT p.Leu265= Benign ★★ 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/srrt-p-arg354trp (accessed [today's date]).

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