Is CMIP p.Thr70Ser (c.209C>G) pathogenic?

CMIP p.Thr70Ser (c.209C>G) is classified Uncertain significance in CMIP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: ambiguous (0.351); Absent from gnomAD v4.1.

How common is CMIP p.Thr70Ser (c.209C>G) in the general population?

CMIP p.Thr70Ser (c.209C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CMIP p.Thr70Ser (c.209C>G)?

AlphaMissense predicts ambiguous (score 0.351) — an in-silico prediction, not a clinical call.

CMIP p.Thr70Ser

c.209C>G · rs1905769827 · VCV2265699

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.351 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.351	ambiguous
REVEL	0.058	moderately benign-leaning
SaProt	LLR -5.05	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 1.6, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 233 kb · p 6.1e-08 · regional, not allelic
Overall
CADD	22.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CMIP
Protein: p.Thr70Ser
Coding: c.209C>G
MANE Select: NM_198390
dbSNP: rs1905769827
Type: single nucleotide variant
Location: chr16:81445450 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.52
Residue 70: the ph domain

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

Similar variants

CMIP c.1638+10G>A Likely benign ★★ same type
CMIP c.2269-10C>T Benign/Likely benign ★★ same type
CMIP p.Asn295= Benign ★★ same type
CMIP p.Leu369= Likely benign ★★ same type
CMIP p.Pro414= Benign ★★ same type
CMIP p.Val547= Benign ★★ same type
CMIP c.1035-1G>A Uncertain significance ★ same type
CMIP p.Ala113Thr 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/cmip-p-thr70ser (accessed [today's date]).

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