Is SRRT p.Arg210Trp (c.628C>T) pathogenic?

SRRT p.Arg210Trp (c.628C>T) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-23). AlphaMissense: likely benign (0.2179); Very rare (popmax 0.00691%, amr).

How common is SRRT p.Arg210Trp (c.628C>T) in the general population?

SRRT p.Arg210Trp (c.628C>T) is very rare (popmax 0.00691%, amr) (gnomAD).

What do computational predictors say about SRRT p.Arg210Trp (c.628C>T)?

AlphaMissense predicts likely benign (score 0.2179) — an in-silico prediction, not a clinical call.

SRRT p.Arg210Trp

c.628C>T · VCV4175249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2179 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00691%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2179	likely benign
REVEL	0.223	benign-leaning
SaProt	LLR -13.66	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -1.5, phastCons 0.99
Regional constraint	o/e 0.76	unconstrained · MANE · 8,778 bp · p 8.1e-06 · regional, not allelic
Overall
CADD	26.2	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

Grpmax group 0.00691% Admixed American · 4/57,872 alleles

Filtering AF 0.0024% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00286% 46/1,609,288 alleles · very rare exomes 42/1,456,976 · genomes 4/152,312 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00691%	14,468
European (non-Finnish)	0.00322%	31,021
Remaining individualsnot grpmax-eligible	0.00321%	31,135
East Asian	0.00223%	44,832
South Asian	0.0011%	90,604

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: SRRT
Protein: p.Arg210Trp
Coding: c.628C>T
MANE Select: NM_015908
Type: single nucleotide variant
Location: chr7:100884110 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 210: an α-helix

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

Similar variants

SRRT p.Arg210Gln 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-arg210trp (accessed [today's date]).

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