Is IQCE p.Pro660Ser (c.1978C>T) pathogenic?

IQCE p.Pro660Ser (c.1978C>T) is classified Uncertain significance in IQCE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.0691); Ultra-rare (popmax 0.0166%, mid).

How common is IQCE p.Pro660Ser (c.1978C>T) in the general population?

IQCE p.Pro660Ser (c.1978C>T) is ultra-rare (popmax 0.0166%, mid) (gnomAD).

What do computational predictors say about IQCE p.Pro660Ser (c.1978C>T)?

AlphaMissense predicts likely benign (score 0.0691) — an in-silico prediction, not a clinical call.

IQCE p.Pro660Ser

c.1978C>T · rs368687600 · VCV2383407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0691 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0166%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0691	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -6.43	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 -0.18	GERP 2.2
Regional constraint	o/e 1.15	unconstrained · MANE · 51 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	7.855	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 0.0166% Middle Eastern · 1/6,012 alleles

Filtering AF 0.00703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00647%

Overall 0.00731% 116/1,587,802 alleles · ultra-rare exomes 105/1,435,572 · genomes 11/152,230 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0166%	6,012
Remaining individualsnot grpmax-eligible	0.00974%	10,264
South Asian	0.00884%	11,312
European (non-Finnish)	0.00839%	11,918
Admixed American	0.005%	19,987
African / African-American	0.00134%	74,580

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.Pro660Ser
Coding: c.1978C>T
MANE Select: NM_152558
dbSNP: rs368687600
Type: single nucleotide variant
Location: chr7:2610052 (GRCh38)
Gene constraint: LOEUF 1.442 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.36
Residue 660: the 'disordered' region

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-pro660ser (accessed [today's date]).

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