Is IQCE p.Ser355Arg (c.1065C>G) pathogenic?

IQCE p.Ser355Arg (c.1065C>G) is classified Uncertain significance in IQCE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-21). AlphaMissense: likely benign (0.2174); Very rare (popmax 0.00133%, afr).

How common is IQCE p.Ser355Arg (c.1065C>G) in the general population?

IQCE p.Ser355Arg (c.1065C>G) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about IQCE p.Ser355Arg (c.1065C>G)?

AlphaMissense predicts likely benign (score 0.2174) — an in-silico prediction, not a clinical call.

IQCE p.Ser355Arg

c.1065C>G · rs2534108558 · VCV2604618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2174	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.53	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 0.16	GERP -3.1, phastCons 0.001
Regional constraint	o/e 1.15	unconstrained · MANE · 51 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	16.92	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 0.00133% African / African-American · 1/75,046 alleles

Overall 6.2e-05% 1/1,613,888 alleles · very rare exomes 1/1,461,570 · genomes 0/152,318 · joint denominator

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: IQCE
Protein: p.Ser355Arg
Coding: c.1065C>G
MANE Select: NM_152558
dbSNP: rs2534108558
Type: single nucleotide variant
Location: chr7:2589927 (GRCh38)
Gene constraint: LOEUF 1.442 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.36

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

Similar variants

IQCE p.Lys538Arg Uncertain significance ★★ ⚠ same type
IQCE p.Asp645= Benign/Likely benign ★★ same type
IQCE p.Leu277= Benign/Likely benign ★★ same type
IQCE p.Pro586Ser Likely benign ★★ same type
IQCE p.Met1Ile Likely pathogenic ★ same type
IQCE p.Trp498Ter Pathogenic ★ same type
IQCE p.Tyr255Ter Pathogenic ★ same type
IQCE c.1440+1G>T 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/iqce-p-ser355arg (accessed [today's date]).

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