Is SRRT p.Pro650Gln (c.1949C>A) pathogenic?

SRRT p.Pro650Gln (c.1949C>A) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely pathogenic (0.9826); Absent from gnomAD v4.1.

How common is SRRT p.Pro650Gln (c.1949C>A) in the general population?

SRRT p.Pro650Gln (c.1949C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SRRT p.Pro650Gln (c.1949C>A)?

AlphaMissense predicts likely pathogenic (score 0.9826) — an in-silico prediction, not a clinical call.

SRRT p.Pro650Gln

c.1949C>A · VCV3962344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9826 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9826	likely pathogenic
REVEL	0.599	indeterminate
SaProt	LLR -13.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,248 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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.Pro650Gln
Coding: c.1949C>A
MANE Select: NM_015908
Type: single nucleotide variant
Location: chr7:100887174 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 650: an α-helix

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

Similar variants

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
SRRT p.Ala190Val Uncertain significance ★ ⚠ 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-pro650gln (accessed [today's date]).

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