Is IQCD p.Ala205Val (c.614C>T) pathogenic?

IQCD p.Ala205Val (c.614C>T) is classified Uncertain significance in IQCD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.1126); Ultra-rare (popmax 0.0165%, mid).

How common is IQCD p.Ala205Val (c.614C>T) in the general population?

IQCD p.Ala205Val (c.614C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about IQCD p.Ala205Val (c.614C>T)?

AlphaMissense predicts likely benign (score 0.1126) — an in-silico prediction, not a clinical call.

IQCD p.Ala205Val

c.614C>T · VCV3529693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1126 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.1126	likely benign
REVEL	0.013	strongly benign-leaning
SaProt	LLR -6.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.8	GERP -2.4, phastCons 0.59
Overall
CADD	10.59	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 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00143% 23/1,613,922 alleles · ultra-rare exomes 19/1,461,746 · genomes 4/152,176 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Finnishnot grpmax-eligible	0.00781%	12,798
Admixed American	0.00167%	60,002
European (non-Finnish)	0.00127%	78,660
South Asian	0.0011%	91,086

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: IQCD
Protein: p.Ala205Val
Coding: c.614C>T
Type: single nucleotide variant
Location: chr12:113207553 (GRCh38)

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

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/iqcd-p-ala205val (accessed [today's date]).

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