Is SRRT p.Ile618Val (c.1852A>G) pathogenic?

SRRT p.Ile618Val (c.1852A>G) is classified Uncertain significance in SRRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-01). AlphaMissense: likely benign (0.0886); Very rare (popmax 0.004%, afr).

How common is SRRT p.Ile618Val (c.1852A>G) in the general population?

SRRT p.Ile618Val (c.1852A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about SRRT p.Ile618Val (c.1852A>G)?

AlphaMissense predicts likely benign (score 0.0886) — an in-silico prediction, not a clinical call.

SRRT p.Ile618Val

c.1852A>G · VCV3962333

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0886 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0886	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -8.29	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.7, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 2,248 bp · p 3.6e-06 · regional, not allelic
Overall
CADD	16.37	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,938 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00116%

Overall 0.00204% 33/1,614,082 alleles · very rare exomes 27/1,461,890 · genomes 6/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,979
South Asian	0.00329%	30,363
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00203%	49,169
Admixed American	0.00167%	59,996

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.Ile618Val
Coding: c.1852A>G
MANE Select: NM_015908
Type: single nucleotide variant
Location: chr7:100887077 (GRCh38)
Gene constraint: LOEUF 0.404 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 66.61 · 6 PDB
Residue 618: an α-helix

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

Similar variants

SRRT p.Ile618Met 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-ile618val (accessed [today's date]).

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