Is CATIP p.Val70Met (c.208G>A) pathogenic?

CATIP p.Val70Met (c.208G>A) is classified Uncertain significance in CATIP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.2903); Very rare (popmax 0.005%, amr).

How common is CATIP p.Val70Met (c.208G>A) in the general population?

CATIP p.Val70Met (c.208G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CATIP p.Val70Met (c.208G>A)?

AlphaMissense predicts likely benign (score 0.2903) — an in-silico prediction, not a clinical call.

CATIP p.Val70Met

c.208G>A · VCV4648583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2903	likely benign
REVEL	0.283	benign-leaning
SaProt	LLR -10.05	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.1	GERP 0.94, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 11 kb · p 0.75 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 0.005% Admixed American · 3/60,000 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000682% 11/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,000
Finnishnot grpmax-eligible	0.00312%	32,006
East Asian	0.00223%	44,886
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000339%	294,999

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: CATIP
Protein: p.Val70Met
Coding: c.208G>A
MANE Select: NM_198559
Type: single nucleotide variant
Location: chr2:218357623 (GRCh38)
Gene constraint: LOEUF 1.144 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.37

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

Similar variants

CATIP p.Ala363Thr Uncertain significance ★★ ⚠ same type
CATIP p.Ser57Leu Uncertain significance ★★ ⚠ same type
CATIP p.Phe35Ile Likely pathogenic ★ ⚠ same type
CATIP p.Ala348Thr Uncertain significance ★ ⚠ same type
CATIP p.Arg187Gln Uncertain significance ★ ⚠ same type
CATIP p.Arg195Cys Uncertain significance ★ ⚠ same type
CATIP p.Arg311Gln Uncertain significance ★ ⚠ same type
CATIP p.Arg383Gly 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/catip-p-val70met (accessed [today's date]).

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